Oncol Res Treat

43(suppl 1) VII–265 (2020) 43 | S1 | 20 print

ISSN 2296–5270

online

e-ISSN 2296–5262

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e-ISBN 978-3-318-06686-9

ABSTRACTS

Band 43,

Supplement 1,

Februar 2020

online only

34. Deutscher Krebskongress

informativ. innovativ. integrativ.

Optimale Versorgung für alle.

Berlin, 19.–22. Februar 2020

Herausgeber

Andreas Hochhaus, Jena

S. Karger

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Inhalt

2018

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2018

Deutsche Gesellschaft für Hämatologie und

Medizinische Onkologie e.V.

Österreichische Gesellschaft für

Hämatologie & Medizinische Onkologie

Österreichische Gesellschaft für

Hämatologie & Medizinische Onkologie e.V.

Schweizerische Gesellschaft für Hämatologie

Arbeitsgemeinschaft Internistische Onkologie in

der Deutschen Krebsgesellschaft e. V. (AIO)

Ocial Organ of Editor-in-Chief

M. Hallek, Cologne

Associate Editors

C. Belka, Munich

M. von Bergwelt, Munich

C. Berking, Munich

C. Bokemeyer, Hamburg

M. Borner, Bern

C. Bruns, Cologne

J. Chemmitz, Koblenz

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A. Reinacher-Schick, Bochum

M. Schlaeppi, St. Gallen

M. Schmidt, Mainz

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M. Theobald, Mainz

M. Thomas, Heidelberg

S. Eckhardt (1978–1989), R. Gross (1978–1980), J.H. Holzner (1978–1990), N. Jaeger (1978–1980),

K. Munk (1978–1980), G.P. Murphy 1978–1980), J.P. Obrecht (1978–1979), A. Stacher (1978–1980),

St. Tanneberger (1978–1980), W. Wilmanns (1978–1980), H. Wrba (1978–1980), G.A. Nagel (1981–1988),

W. Queißer (1989–2002), W. Huber (1992–1998), H.-J. Schmoll (2002–2012)

U. Wedding, Jena

W. Wick, Heidelberg

Editorial Board

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D. Arnold, Hamburg

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N. Skoetz, Cologne

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J. Werner, Munich

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Member of Deutsche Krebsgesellschaft e.V.

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Disclosure Statement

The Editor declares that he has no conict of interest.

Impressum

Inhalt

2018

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2018

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Inhalt

2018

Index

2018

Band 43,

Supplement 1,

Februar 2020

online only

Herausgeber

Andreas Hochhaus, Jena

Supplement 1/2020

e-ISBN 978-3-318-06686-9

Basel . Freiburg . Hartford . Oxford . Bangkok . Dubai . Kuala Lumpur .

Melbourne . Mexico City . Moscow . New Delhi . Paris . Shanghai . Tokyo

34. Deutscher Krebskongress

informativ. innovativ. integrativ.

Optimale Versorgung für alle.

Berlin, 19. – 22. Februar 2020

ABSTRACTS

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Oncol Res Treat 2020;43(suppl 1):IV

Kongresspräsident Prof. Dr. Andreas Hochhaus (Jena)

Kongresssekretäre Dr. Tobias Rachow (Jena)

Dr. Philipp Ernst; M.Sc. (Jena)

Dr. Ulrike Laubscher (Jena)

Svetlana Scherübl (Jena)

Gutachter Gerhard Adam (Hamburg); Hojjat Ahmadzadehfar (Bonn); Hakan Alakus (Köln); Udo

Altmann (Gießen); Dirk Arnold (Hamburg); Ulli Simone Bankstahl (Frankfurt/M.);

Sebastian Bauer (Essen); Freerk Baumann (Köln); Jürgen Christian Becker

(Heidelberg); Carola Berking (München); Carsten Bokemeyer (Hamburg); Kerstin

Bornemann (Göttingen); Thomas Brabletz (Erlangen); Jens Büntzel (Nordhausen)

Reinhard Büttner (Köln); Gamze Damnali (Landhut); Maike de Wit (Berlin); Thomas

Decker (Ravensburg Carsten Denkert (Marburg); Andreas Dinkel (München);

Wilfried Eberhardt (Essen); Matthias Ebert (Mannheim); Nadja Ebert (Heidelberg);

Franziska Eckert (Tübingen); Rainer Engers (Neuss); Thomas Ernst (Jena); Philipp

Ernst (Jena); Emmanouil Fokas (Frankfurt/M.); Annette Freidank (Fulda); Simone

Fulda (Frankfurt/M.); Deniz Gencer (Mannheim); Michael Ghadimi (Göttingen); Ines

Gockel (Leipzig); Thorsten Götze (Frankfurt/M.); Paul Graf La Rosée (Villingen-

Schwenningen); Marc-Oliver Grimm (Jena); Christian Grohé (Berlin); Thomas

Gronau (Bendorf); Viktor Grünwald (Essen); Orlando Guntinas-Lichius (Jena); Ralf

Gutzmer (Hannover); Christian Habermann (Hamburg); Andreas Hochhaus (Jena);

Jens Ho󰀨mann (Berlin); Jürgen Ho󰀨mann (Heidelberg); Wilfried Ho󰀨mann

(Badenweiler); Wolfgang Ho󰀨mann (Greifswald); Ralf-Dieter Hofheinz (Mannheim);

Wolf-Karsten Hofmann (Mannheim); Uta Höpken (Berlin); Lars-Christian Horn

(Leipzig); Markus Horneber (Nürnberg); Gerdt Hübner (Oldenburg); Jutta Hübner

(Jena); Christian Jackisch (O󰀨enbach); Klaus-Peter Janssen (München); Karin

Jordan (Heidelberg); Meinolf Karthaus (München); Christian Keinki (Jena); Jens

Peter Klußmann (Köln); Gabi Knötgen (Aurich); Alfred Königsrainer (Tübingen);

Mechthild Krause (Dresden); Matthias Kroiss (Würzburg); Thomas W. Kubin

(Traunstein); Sherko Kümmel (Essen); Annette Lebeau (Hamburg); Hartmut Link

(Kaiserslautern); Diana Lüftner (Berlin); Christian Mawrin (Magdeburg); Anja

Mehnert-Theuerkauf (Leipzig); Susanne Merkel (Erlangen); Oliver Micke (Bielefeld);

Matthias Naegele (Zürich); Jens Neumann (München); Petra Ortner (München);

Friedrich Overkamp (Hamburg); Thorsten Persigehl (Köln); Uwe Platzbecker

(Leipzig); Franz-Josef Prott (Wiesbaden); Tobias Rachow (Jena); Martin Reck

(Großhansdorf); Christian Reinhardt (Köln); Oliver Rick (Bad Wildungen); Anja Rinke

(Marburg); Christoph Ritter (Greifswald); Andreas Rosenwald (Würzburg); Amir

Sabet (Frankfurt/M.); Uwe Schlegel (Bochum); Harald Schmalenberg (Dresden);

Thorsten Schmidt (Kiel); Tilman Schöning (Freiburg); Jalid Sehouli (Berlin); Christine

Sers (Berlin); Thomas Seu󰀨erlein (Ulm); Thorsten Simon (Köln); Marianne Sinn

(Hamburg); Jens Siveke (Essen); Sigrun Smola (Homburg); Christine Spitzweg

(München); Annette Stäbler (Tübingen); Monika Steimann (Boltenhagen); Joachim

P. Steinbach (Frankfurt/M.); Konrad Steinestel (Ulm); Sebastian Stintzing (Berlin);

Andrea Tannapfel (Bochum); Michael Thomas (Heidelberg); Peter Thuss-Patience

(Berlin); Amanda Tufman (München); Beate Volkmer (Buxtehude); Marie von

Lilienfeld-Toal (Jena); Arend von Stackelberg (Berlin); Cornelius Waller (Freiburg);

Stefanie Walter (Bonn); Eva Wardelmann (Münster); Ulrich Wedding (Jena);

Wolfgang Wick (Heidelberg); Elisabeth Wiesmüller (Ulm); Olaf Witt (Heidelberg);

Andrea Wittig Jena Barbara Wollenberg (Lübeck); Tanja Zimmermann (Hannover);

Johannes Zuber (Wien)

Inhalt

2018

Index

2018

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Oncol Res Treat 2020;43(suppl 1):V

Inhalt

Best-of-Abstracts-Vorträge

Basic Research 1

Developmental Therapeutics: Immunotherapy/Cellular Therapy 39

Developmental Therapeutics: Molecular Therapeutics 42

Gastrointestinal (Colorectal) Cancer 47

Gastrointestinal (Noncolorectal) Cancer 58

Genito-urinary Cancer, including Prostate Cancer 69

Gynecological Cancer 87

Leukemia, Myelodysplasia, Transplantation 104

Translational Oncology 197

Other Topics 204

Inhalt

2018

Index

2018

Oncol Res Treat 2020;43(suppl 1):VI

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Inhalt

Late-Breaking Abstracts

Vorträge

Cancer Prevention 211

Developmental Therapeutics: Immunotherapy/Cellular Therapy 213

Gastrointestinal (Colorectal) Cancer 218

Gastrointestinal (Noncolorectal) Cancer 220

Head and Neck Cancer 230

Lung Cancer 232

Lymphoma and Plasma Cell Disorders 238

Poster

Breast Cancer 209

Cancer Prevention 211

Central Nervous System Tumors 212

Developmental Therapeutics: Cytotoxic Chemotherapy 213

Developmental Therapeutics: Molecular Therapeutics 216

Epidemiology 218

Gastrointestinal (Colorectal) Cancer 218

Gastrointestinal (Noncolorectal) Cancer 220

Genito-urinary Cancer, including Prostate Cancer 224

Geriatric Oncology 227

Head and Neck Cancer 230

Immunotherapy Side Eects 231

Lung Cancer 232

Pediatric Cancer 238

Palliative Care 240

Psychooncology 240

Radiation 242

Rehabilitation and Long-term Burden in Social Medicine (Survivor) 242

Sarcoma 243

Skin Cancer, including Melanoma 243

Supportive Care 244

Autorenindex 247

Impressum II

Oncol Res Treat 2020;43(suppl 1):VII

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Abstracts

Inhalt

2018

Index

2018

E-Mail karger@karger.com

www.karger.com/ort

Basic Research

Best-of-Abstracts-Vorträge

528

The Oncogenic MDm4 Protein acts as a Supporter

of DNA-Replication

Kai Wohlberedt 1; Ina Klusmann 1; Polina Derevyanko 1;

Valentina Manzini 1; Celeste Giansanti 1; Josephine Choo 1;

Anna Magerhans 1; Christine Eischen 2; Aart Jochemsen 3;

Matthias Dobbelstein 1

1Institute of Molecular Oncology, University Medical Center Göttingen,

Deutschland

2Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas

Jeerson University Philadelphia, United States

3Department Cell and Chemical Biology, Leiden University Medical Center,

Niederlande

Purpose: e Mdm4 (alias Mdmx) oncoprotein heterodimerizes with

Mdm2 and together they antagonize the tumor suppressor p53. p53-inde-

pendent activities of the two Mdm proteins are emerging, and we have re-

ported the ability of Mdm2 to modify chromatin [1] and to support DNA

replication by suppressing the formation of DNA/RNA hybrids (R-loops)

[2]. We asked whether Mdm4 can also contribute to an unperturbed DNA

replication fork progression.

Methods: Quantication of the speed and processivity of single DNA rep-

lication forks in tumor-derived as well as non-transformed cell lines was

assessed by DNA ber assays upon removal of Mdm4. Immunoblots and

immunouorescence microscopy allowed us to determine indicators of

replicative stress. Cell proliferation assays and cytometry following EdU

incorporation were used to investigate cell survival and overall DNA syn-

thesis.

Results: e loss of Mdm4 in p53-decient cells strongly impaired DNA

replication fork progression. Co-depletion of Mdm4 and Mdm2 com-

promised DNA replication even further, arguing that they act through

partially distinct mechanisms. Further analysis revealed that the RING

domain of Mdm4 was necessary to ensure DNA replication fork pro-

gression. By inducing the formation of DNA/RNA hybrids, Mdm4 de-

pletion signicantly increased replication stress. Due to elevated ring of

replication origins, loss of Mdm4 only marginally aected cell prolifera-

tion but sensitized p53-/- cells to the nucleoside analogue gemcitabine.

Conclusions: Mdm4 supports DNA replication by preventing the ac-

cumulation of DNA/RNA hybrids independent of p53. ese ndings

suggest a new route of chemosensitization with low toxicity using Mdm4

inhibitors and further support Mdm4 as a therapeutic target in cancer.

References:

1. Wienken et al., Molecular Cell 2016

2. Klusmann et al., PNAS 2018

Disclosure Statement: e authors declare no conict of interest.

Poster

146

Dierences in Mitochondria between Normal and Cancer Cells

as Molecular Cancer Target

Alexander Gosslau

City University of New York, Department of Biology, New York, United States

Purpose: Cancer prevention therapies with an induction of apoptosis in

cancer cells with least adverse eects on normal cells is a particularly de-

sirable strategy in cancer research.

Methods: Fluorescence, transmission and scanning electron microscopy,

Immunohistochemistry, RT-PCR, Western Blot analysis.

Results: We demonstrated that a matched pair of isogenetic normal

and transformed counterpart cells (WI38/WI38VA) showed a selective

induction of the mitochondrial-mediated apoptotic pathway only in

tumor but not in normal cells in response to resveratrol analogs, black tea-

derived theaavins, and oxidative stress. Tumor cells bearing a bubble-like

mitochondrial network showed intrinsic apoptosis in response to various

inducers. In contrast, normal counterpart cells or tumor cells which

were resistant to apoptosis were composed of a web-like mitochondrial

reticulum.

Conclusions: In summary, our results indicate a correlation between

mitochondrial morphology and the capacity for induction of apoptosis.

Knowledge about mitochondrial morphology or cellular components

impacting mitochondria (e.g. microtubule) thus oer a unique molecu-

lar site against which selective natural-derived bioactives and/or physi-

co-chemical inducers might be targeted.

Relevant References:

1. Gosslau, A., Pabbaraja, S., Knapp, S., and Chen, K.Y. (2008) Trans- and

cis-stilbene polyphenol derivatives induced rapid perinuclear mitochondrial

clustering and p53-independent apoptosis in cancer cells but not normal cells.

Eur. J. Pharmacol., 587, 25-34

2. Gosslau, A., and Chen, K.Y. (2004) Nutraceuticals, apoptosis, and disease

prevention. Nutrition 20, 95-102 (Review)

Disclosure Statement:

Relevant nancial relationships:

Professor, Dept. of Science (Biology), City University of New York, BMCC

Relevant non-nancial relationships:

Visiting Professor, Dept. of Food Science, Rutgers University, New Brunswick,

New Jersey

Editorial Board member, Movement and Nutrition in Health and Disease

Associate Editor-in-Chief, Food Science and Human Wellness

Oncol Res Treat 2020;43(suppl 1):1–265

DOI: 10.1159/000506491

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts2

Inhalt

2018

Index

2018

443

Mechanisms of Mitigating Aneuploidy-Induced Telomere

Replication Stress by Telomerase

Sabine Meessen 1; Sebastian Iben 2; Anca Azoitei 1; Sebastian Wiese 3;

Christian Bolenz 4; Cagatay Günes 1

1Urologie und Kinderurologie, Universitätklinikum Ulm, Ulm, Deutschland

2Dermatologie und Allergologie, Universitätsklinikum Ulm , Ulm

3Core Unit Mass Spectrometry an Proteomics, Universitätsklinikum Ulm, Ulm

4Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Ulm,

Deutschland

Purpose: Aneuploidy represents a hallmark feature of carcinogenesis in

humans but mutations in the canonical ploidy-control genes are rare as

these mutations impair cell tness. Recent data indicate that aneuploidy

can inhibit or instigate tumorigenesis dependent on the genetic back-

ground. ese observations imply that aneuploidy can be induced by

non-canonical ploidy-control mechanisms and tumor cells activate mech-

anisms to allow survival of aneuploid cells. We have recently identied

non-canonical ploidy-control genes and could show that telomerase rep-

resents an aneuploidy survival mechanism. We aim to elucidate the path-

ways of canonical and non-canonical aneuploidy induction and the mech-

anisms how telomerase suppresses aneuploidy-induced cell senescence.

Methods: Knockdown or knockout of MAD2 (canonical ploidy-control

gene) or ORP3 (non-canonical ploidy control gene) is achieved in telo-

merase positive and telomerase negative human broblasts by shRNAs or

the CRISPR-Cas9 technology. e replication stress is evaluated by immu-

nouorescence staining of p-RPA2, an established marker for replication

stress. We further use proteome analyses to answer the question whether

telomerase itself is sucient to suppress aneuploidy-induced replication

stress or whether it requires cooperation partners for this process.

Results: e knockdown and knockout of ORP3 induces aneuploidy in

both, telomerase negative and positive cells. As reported previously, aneu-

ploidy induction resulted in increased replication stress and impairment

of cell proliferation in telomerase negative primary human broblasts (BJ)

while ectopic expression of telomerase in these cells (BJ-hTERT) sup-

presses aneuploidy-induced replication stress. Initial results indicate the

involvement of helicases mitigating aneuploidy-induced replication stress

and to allow continuous proliferation of aneuploid cells.

Conclusions: e data indicate that telomerase requires cooperation

partners, such as helicases, to suppress to suppress aneuploidy-induced

replication stress.

449

Identication of Microvesicle-Specic Proteins and their

Implications in Vesicle Biogenesis

Cedric Weich 1; Leon Kaiser 2; Matthias Schulz 2; Hanibal Bohnenberger 3;

Christof Lenz 4; Claudia Binder 2; Annalen Bleckmann 1, 2; Kerstin Menck 1, 2

1Universitätsklinikum Münster, Medizinische Klinik A, Münster, Deutschland

2Universitätsmedizin Göttingen, Klinik für Hämatologie/Medizinische

Onkologie, Göttingen, Deutschland

3Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland

4Universitätsmedizin Göttingen, Institut für Klinische Chemie, Göttingen,

Deutschland

Purpose: Extracellular vesicles are increasingly recognized as important

mediators of intercellular communication and biomarkers in cancer. ey

are divided into two main populations, the small exosomes (Exo, diame-

ter <150 nm) that derive from multivesicular endosomes, and larger mi-

crovesicles (MV, diameter 100-1000 nm) that bud o directly from the

cell membrane. While key regulators of Exo secretion have been recently

identied, the biogenesis of MV is barely understood. erefore, the aim

of this study was to identify novel MV proteins that might play a role in

MV biogenesis.

Methods: We isolated MV and Exo from SK-BR-3 breast cancer cells and

used SILAC (stable isotope labeling by/with amino acids in cell culture)

followed by mass spectrometry to compare their proteome. MV-specic

proteins were validated by Western Blot and analyzed for their eect on

MV biogenesis.

Results: Comparison of the MV and Exo proteome revealed 171 proteins

to be signicantly dierentially expressed, among them many proteins as-

sociated with cytoskeletal organization that were exclusively present on

MV. We validated the expression of these proteins on MV and Exo from

several breast cancer as well as normal cell lines and showed that Rgap1,

Prc1 and Kif4a were indeed expressed specically on MV from all cells.

Knockdown of these proteins by siRNA in SK-BR-3 cells and subsequent

analysis of their secreted vesicles by Western Blot and Nanoparticle Track-

ing Analysis suggested that the three proteins were indeed involved in MV

biogenesis. Interestingly, all three proteins are associated with microtu-

bules and play an important role in cytokinesis. erefore, our ongoing

research focuses on analyzing the intracellular expression and co-localiza-

tion of the identied markers with other known MV-specic proteins as

well as studying the inuence of microtubule inhibitors on MV biogenesis.

Conclusions: Taken together, our results identied 3 novel regulators of

MV biogenesis and suggest that microtubules are involved in this process.

Disclosure Statement: e authors have nothing to disclose.

459

The Non-Canonical WNT Ligand-Receptor Pair WNT11/

ROR2 Mediates Breast Cancer Invasion through RHOA/ROCK

Signaling

Kerstin Menck 1, 2; Saskia Heinrichs 1, 2; Maren Sitte 3; Tim Beissbarth 3;

Helen Noeding 4; Andreas Jansho 4; Claudia Binder 2;

Annalen Bleckmann 1, 2

1Universitätsklinikum Münster, Medizinische Klinik A, Münster, Deutschland

2Universitätsmedizin Göttingen, Klinik für Hämatologie/Med. Onkologie,

Göttingen, Deutschland

3Universitätsmedizin Göttingen, Institut für Medizinische Bioinformatik,

Göttingen, Deutschland

4Georg-August-Universität Göttingen, Institut für Physikalische Chemie,

Göttingen, Deutschland

Purpose: Breast cancer (BC) is the second most common tumor entity

worldwide. Tumor progression leads to the formation of metastases for

which there is still no curative therapy. Several studies have suggested that

BC metastasis involves activation of the Wnt pathway. In this study we

aimed to identify novel pathways members involved in BC progression.

Methods: Gene expression data from BC patients were analyzed for

the expression of Wnt proteins associated with metastasis. Candidate

proteins were modulated for their expression in cell lines and their role

in tumor progression was analyzed by functional assays and molecular

characterization.

Results: Using a targeted analysis of gene expression data from BC pri-

mary tumors and metastases, we found that especially the β-catenin inde-

pendent, non-canonical Wnt signaling pathway is active in metastases and

associated with poor survival. In particular the non-canonical Wnt recep-

tor Ror2 was found to be highly expressed in BC brain metastases and was

associated with worse metastasis-free survival. To understand the molec-

ular basis for these observations, we overexpressed Ror2 in human BC cell

lines which led to an increase in tumor invasion that was dependent on

increased RhoA and Rock expression. Ror2-overexpressing cells showed

defects in cell morphology and cell-cell contacts in microscopic assays as

well as Electric Cell-Substrate Impedance Sensing (ECIS) measurements.

In order to identify the ligand responsible for these changes, cells were

characterized by RNA-Seq and real-time PCR which revealed an upregu-

lation of the non-canonical Wnt11 ligand. Co-immunoprecipitation con-

rmed that Wnt11 acted as a novel ligand for Ror2. Wnt11 activated Rock

signaling and its knockdown reversed the pro-invasive phenotype and

changes in Ror2-overexpressing cells. High Wnt11 levels in primary BC

patient samples were associated with poor metastasis-free survival.

Conclusions: Our study has revealed Wnt11/Ror2 as a novel target driv-

ing tumor invasion and progression in BC.

Disclosure Statement: e authors have nothing to disclose.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 3

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2018

Index

2018

526

CXCR4LASP1 Interaction – Dierences between Breast

Cancer and CML

Jochen Frietsch 1; Andreas Herrmann 2; Cristina Peperina Viciano 3;

Andreas Hochhaus 1; Thomas Ernst 1; Carsten Homann 4; Alma Zernecke 2;

Elke Butt 2

1Universitätsklinikum Jena, Klinik für Innere Medizin II, Abteilung für

Hämatologie und Internistische Onkologie, Jena, Deutschland

2Universitätsklinikum Würzburg, Institut für Experimentelle Biomedizin II

Würzburg

3Universitätsklinikum Würzburg, Rudolf-Virchow-Zentrum für Experimentelle

Biomedizin, Würzburg

4Universitätsklinikum Jena, Institut für Molekulare Zellbiologie, Jena

Purpose: CXCR4 has been reported to play an important role in cell sur-

vival, proliferation, migration, as well as metastasis of tumors. Activation

by SDF-1 activates PI3K/AKT signaling. In breast cancer (BC), overex-

pression of CXCR4 is involved in directing metastasis of CXCR4 positive

tumor cells to organs producing SDF-1. In CML, CXCR4 is down-regulat-

ed by BCRABL causing defective adhesion of CML cells to bone marrow

stroma.

Recently, the cytoskeletal and adaptor protein LASP1 was described as a

novel CXCR4 binding partner and a promoter of the PI3K/AKT pathway.

We sought to investigate the LASP1-CXCR4 axis in solid and hematopoi-

etic malignancy and propose a model in which both signaling pathways

are interconnected.

Methods: MDAMB-231 BC and K562 CML cells were used to investigate

the phosphorylation-dependent dierences in binding of LASP1 to CXCR4

by immunoblotting, pull-down experiments and immunouorescence

staining. Cells with knockdown of CXCR4/LASP1 as well as CXCR4-CFP/

Venus-LASP overexpressing HEK293 cells were employed for probing

CXCR4-LASP1 signaling.

Results: In BC cells, overexpressed LASP1 shows S146 phosphorylation

and nuclear translocation whereas in advanced CML, the protein is down-

regulated and Y171 hyperphosphorylation is observed.

Binding of LASP1 to CXCR4 only occurs aer S146 phosphorylation. e

phosphorylation is transient: Upon CXCR4 stimulation, dephosphoryla-

tion of LASP1 at the PKA-site (S146) and concomitant phosphorylation

at Y171 by TKs occurs. Opposite eects are observed in CXCR4 decient

CML cells treated with TKI to block BCR-ABL.

Conclusions: In BC cells, binding of pLASP1-S146 stabilizes the C-tail

of the CXCR4 and hinders the phosphorylation at multiple PKC serine

phosphorylation sites important for receptor internalization. In contrast,

increased LASP1-Y171 phosphorylation by BCR-ABL renders the protein

less ane to the CXCR4 C-terminus, and facilitates serine and tyrosine

phosphorylation, resulting in down-regulation of CXCR4 and causing de-

fective adhesion of CML cells to bone marrow stroma.

Disclosure Statement: EB and JF have received grants from the German Cancer

Aid (Project numbers: 70112717 and 70112142).

e authors declare no conicts of interests.

551

IL17A+ CD4+ T Cell Heterogeneity in Colorectal Cancer

Leonie Konczalla 1; Filippo Cortesi 1; Tabea Sturmheit 2; Anna Wöstemeier 1;

Jenny Krause 2; Ramez Wahib 1; Jakob R. Izbicki 1; Daniel Perez 1;

Samuel Huber 2; Nicola Gagliani 1, 2

1Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum

Hamburg-Eppendorf , Hamburg , Deutschland

2II. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg ,

Deutschland

Purpose: Recently, cancer therapy has been overturned by the discovery

of immunotherapies targeting co-inhibitory receptors (CIR) as PD-1.

However, in CRC, immunotherapies did not meet the expectations, as

only a minority benet. We hypothesize that two key factors can contrib-

ute to the poor ecacy in CRC: (I) the functional heterogeneity of the

targeted cells and (II) the local microenvironment.

Methods: Human T cell analysis by FACS, RNAseq, TCRseq and CITE-

seq. Functional tests in murine CRC models with dierent microbiota.

In vitro T cell dierentiation by co culture with 3-dimensional primary

tumor structure.

Results: We show accumulation of dierent subsets of IL-17A+ CD4 T

cells in CRC. One subset is characterized by the co-expression of FoxP3,

the key regulator of anti-inammatory T-cells, and of IL-17A, a pro tum-

origenic cytokine. In line, our murine data suggest strong tumor fostering

activity of IL17A+ FoxP3+ CD4 T cells. Importantly, these cells express

several CIR. erefore, they react to immunotherapy, but in an undesir-

able, tumor supporting manner. In addition, tumor progress is modied

by dierent microbiota. Interaction of CD4 T cells and the microbiome is

of pivotal importance in directing immune response 1. Interestingly, there

is evidence that the microbiota composition impacts the success or failure

of immunotherapy 2. If the microbiota modulates IL-17A+ FoxP3+ CD4

T cell abundance and their CIR pattern needs to be claried. is might

determine the ecacy of immunotherapy.

Conclusions: IL17A+ FoxP3+ CD4 T cells are promoting tumor growth

and express several CIR. If these CIR correlates with a special composition

of the colonic microbiome needs to be elucidated. Characterizing this pro

tumorigenic cell population, we seek to determine the best immunother-

apy regimen for CRC patients.

References:

1. Ivanov, II, et al., Induction of intestinal 17 cells by segmented lamentous

bacteria. Cell, 2009. 139(3): p. 485-98.

2. Gopalakrishnan, V., et al., Gut microbiome modulates response to anti-PD-1

immunotherapy in melanoma patients. Science, 2018.

580

Characterization of Tumor Cell-Derived Extracellular Vesicles

in Liquid Biopsies

Fanny Ender 1; Piet Zamzow 1; Nikolas von Bubno 1; Frank Gieseler 1

1Clinic for Hematology and Oncology, UKSH Lübeck, Lübeck, Deutschland

Purpose: Extracellular vesicles (EVs) are released by eukaryotic cells in-

cluding tumor cells1. Due to their small size (< 1 µm), they can be detect-

ed in all body uids. In order to be used as diagnostic markers in liquid

biopsies, EV subpopulations (e.g. exosomes, ectosomes, apoptotic bodies)

need to be detected and characterized. Here, we share our experiences and

give suggestions for technical improvements.

Methods: We used the human pancreatic cancer cell line COLO357 as a

source for EVs. EV subpopulations were separated by sequential centrif-

ugation based on size and mass. Membranes of intact EVs were labeled

with CFSE and analyzed using a high-resolution ow cytometer as well

as nanoparticle tracking analysis (NTA). According to previous publica-

tions, and in accordance with our observations, cells, cellular debris and

apoptotic bodies were pelleted using (2x) 2.500 x g (low speed). en, an

EV sub-fraction was selectively enriched (ectosomes) by 10.000 x g (high

speed). Nevertheless, a sheer separation of ectosomes and exosomes was

not possible due to overlapping sizes.

Results: Subsequently, we optimized staining conditions and adapted

settings for ow cytometry analysis. While 1 µM CFSE was sucient

for membrane labeling of cells, we now recommend a 40-fold higher

concentration for EVs; of note: unlabeled high-speed EVs were

indistinguishable from background noise. Short incubation times and

stable temperature conditions were of major importance for yielding

intact vesicles. Most important, threshold adjustment of uorescence

channel aected the resolution of CFSE-labeled EVs and thus, signicantly

inuenced EV quantication.

Conclusions: Liquid biopsies embody the future of precision medicine in

oncology. Protocol optimization and standardization for sample collec-

tion, processing and analysis have to be dened precisely for accurate and

comparable results.

Reference:

1. Yáñez-Mó et al., J Extracell Vesicles 2015

Disclosure Statement: e Authors declare no conict of interest.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts4

Inhalt

2018

Index

2018

582

Novel Nanowell-Based Workow for Single Circulating Tumor

Cell Isolation with Cellcelector™

Liwen Yang 1; Mahdi Rivandi 1; André Franken 1; Constantin Nelep 2;

Jens Eberhardt 2; Dieter Niederacher 1; Tanja Fehm 1; Hans Neubauer 1

1Department of Obstetrics and Gynecology, University Hospital of Düsseldorf,

Düsseldorf, Deutschland

2ALS Automated Lab Solutions GmbH, Jena, Deutschland

Purpose: e CellCelector™ system enables the isolation of single circu-

lating tumor cells (CTCs) for comprehensive genomic analysis. However,

although dierent technologies are used to pre-enrich CTCs, high num-

bers of contaminating white blood cells (WBCs) are still impeding single

cell isolation.

In addition, deposition control of isolated CTCs is currently not possi-

ble due to separation of deposition and aspiration areas of CellCelector,

which causes extra costs when empty tubes will be processed e.g. by whole

genome amplication.

We aimed to implement technical solutions to both issues in order to op-

timize and speed-up single cell micromanipulation.

Methods: SKBR3 cells were loaded onto PDMS nano-well chips of dif-

ferent geometries. We tested the size of nano-wells with cavities ranging

from 15µm to 30µm in diameter and determined a) the cell seeding rate

(% of cells captured in nano-wells); b) the cell picking success rate; c) the

cell purity rate (i.e. isolation of the target cell without co-aspiration of cells

in neighbouring well); and d) on chips staining recover rate. Deposition

was veried by microscopic inspection with at bottom tubes. Validation

experiments were done with the patient’s CellSearch sample.

Results: Best cell seeding rates were observed with 30µm nano-wells, with

15µm nano-wells many cells were not captured. e experiments using

30µm wells of dierent geometries are in progress. On-chip staining re-

sulted in a recovery rate of 80%-90%. Deposition control worked to 100%

with 4titudes at bottom tubes. A new adapter for CellCelector was de-

signed and produced to execute this workow on the microscope stage

thereby also increasing the speed of micromanipulation by approx. 50%

to 60%.

Conclusions: We have improved single CTCs isolation with the CellCe-

lector by implementing nano-well chips for cell separation and at bottom

tubes to control cell deposition. Apart from the reduced processing time

this will also reduce the costs caused by unsuccessful cell deposition.

648

Low Dose Irradiation Stimulates Spherogenesis via

Alterations in Cytokine Secretion

Marise Walter-Diessars 1; Diana Freitag 1; Werner Dammermann 2;

Lukas Hain 1; Nasrin Abbasi-Senger 3; Tilo Wiezorek 3; Andrea Wittig 3;

Rolf Kal 1; Jan Walter 1,4

1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland

2University Hospital Brandenburg- Brandenburg Medical School, Center of

Internal Medicine II, Brandenburg, Deutschland

3University Hospital Jena, Department of Radiotherapy and Radiation Oncology,

Jena, Deutschland

4Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken,

Deutschland

Purpose: Ionizing radiation is a known risk factor for the development of

meningiomas. However, the underlying mechanism is largely unknown. It

is discussed whether radiation triggers mutations or (immuno-)modula-

tory processes, that might lead to the dedierentiation of somatic cells and

ultimately to the development of tumor stem cells. e aim of this study

was to investigate the inuence of ionizing radiation on immunomodu-

latory processes in meningioma cells (PMCs) and non-pathological dura

mater cells (DMCs) in vitro.

Methods: ree PMC and three DMC cultures were cultivated under

standard conditions. e conuent monolayers were exposed to a single

dose of photon irradiation (1, 2, 4, 8, 12, 16, 20 Gy). 24h and 7, 14, 21 and

28 days aer treatment, cells were passed and analyzed. Analyses were

performed in respect to morphology (cell shape, generation times, etc.),

molecular biology and immunological aspects .

Results: In the high-dose radiation group (>= 8Gy) morphological anal-

yses showed clear signs of necrosis in all cell types. Under certain condi-

tions all cell types showed a tendency to detach from the subsurface, and

low-dose irradiated cells (<= 4Gy) tended to form spheroids. Compared

to DMS, in PMCs this eect was seen later (7d vs. 21d). In addition, 28d

aer irradiation, DMCs were more sensitive to radiation than PMCs. It

was found that the equivalent experimental group to the IC50 values de-

termined for each culture was also the group with the highest IL6 secre-

tions aer 28d. Further correlations were found between the time of the

maximum IL6 secretions and the occurrence of spheroids in the PMCs.

e IL8 secretion also showed a relation between the replacement of the

cells at spherogenesis by decreasing concentrations.

Conclusions: Based on the presented data, a correlation between the se-

cretion of IL6+IL8 and the formation of stem cell specic spheroids might

be hypothesized. us, it seems possible that a radiation-induced cytokine

secretion may trigger a stem cell-like phenotype formation.

Disclosure Statement: e authors report no conicts of interest.

649

Dened Glucose Levels Stimulate Metabolic Reprogramming

and Tumor Augmenting Processes in Human Meningioma

Cells

Sophie Huppertz 1; Diana Freitag 1; Undine Tiller 1; Rolf Kal 1; Jan Walter 1, 2

1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland

2Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken

Purpose: In contrast to normal mammalian cells, cancer cells use glycol-

ysis to generate energy due to their increased metabolism. is eect has

an important role in carcinogenesis and tumor progression. e extent to

which this also applies to meningiomas has not yet been investigated. e

aim of this study is to investigate the inuence of dierent glucose levels

during glycolysis on tumor-promoting processes in human meningiomas.

Methods: e meningioma cell line Ben Men-1 was cultured 24h in a

glucose-free medium. Aerwards, the metabolic activity was measured

by MTT assay and the proliferation rate by BrdU ELISA under 14

dierent glucose concentrations (0 to 100 mM). A peak tting analysis

was used to determine the concentrations for maximum eect in both

assays. Subsequently, 5 concentrations were determined that promote

maximum, minimum and optimal activities. e cells were seeded at a

density of 6x 105 cells/25cm2 and further cultured under the previously

dened conditions. Doubling times, morphological changes and marker

expression were determined by immunocytochemistry.

Results: A maximum of metabolic activity was seen at glucose concen-

trations of 17.2 mM and 66.7 mM, and maximum proliferation rates

at concentrations of 18.5 mM, 35.6 mM and 57.3 mM. Based on these

facts, meningioma cells were then cultured and analyzed with glucose

concentrations of 0, 15, 40, 65 and 100 mM. It was found that long-term

cultivation (>p4) under 15-65 mM glucose was possible. Cells fed with

65 mM glucose showed the fastest doubling times. e IHC characteri-

zation showed surprisingly decreasing vimentin and EMA signals in the

65 mM group in contrast to the other investigation groups. In addition, we

found increased values for pmTOR and GLUT3.

Conclusions: Our results show that meningioma cells also respond to an

increase in environmental glucose levels with an increased tumor progres-

sion. In particular, the increased expression of GLUT3 and p-mTOR sug-

gests a possible metabolic reprogramming in this context.

Disclosure Statement: e authors report no conicts of interest.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 5

Inhalt

2018

Index

2018

662

Irradiation as a Trigger for Cellular Reprogramming of Human

Meningioma Cells

Lukas Hain 1; Diana Freitag 1; Nasrin Abbasi-Senger 2; Tilo Wiezorek 2;

Andrea Wittig 2; Rolf Kal 1; Jan Walter 1, 3

1University Hospital Jena, Department of Neurosurgery, Jena, Deutschland

2University Hospital Jena, Department of Radiotherapy and Radiation Oncology,

Jena, Deutschland

3Medical Center Saarbruecken, Department of Neurosurgery, Saarbrücken,

Deutschland

Purpose: In previous studies it could be shown that irradiation is a de-

cisive risk factor for the development of meningiomas. e underlying

mechanism is still largely unknown. A promising hypothesis is based on

the existence of tumor stem cells expressing embryonic NANOG1 as well

as tumor-specic NANOGP8 at dierent levels. e aim of this study was

to investigate the eects of ionizing radiation on the induction of plurip-

otent stem cells from primary WHO°I meningioma cells (PMC) in vitro.

Methods: ree PMC cultures were incubated under standard conditions

and subsequently exposed to single dose photon irradiation (1, 2, 4, 8, 12,

16, 20 Gy). Aer 24h the cells were rst passed and cultivated for 9 more

passages or 84d. At the end of the experiment the expression of NANOG

(immunocytochemistry) as well as the secretion of the cytokines IL-6 and

IL-8 were analysed. e dierence between NANOG1 and NANOGP8

mRNA expression was determined.

Results: Especially in the low-dose radiation range (1-4 Gy), PMCs

showed a change in morphological properties towards cell clusters and

spheroid cells, which is a well-known property of stem cells. Additionally,

aer low-dose irradiation, PMCs showed a clear tendency towards faster

growth. Immunocytochemistry showed weak NANOG expression in tu-

mor cells. qPCR showed a signicantly higher expression of the NANOG1

gene variant in the 1 Gy (p=0.038), 2 Gy ( p=0.045) and 4 Gy (p=0.005)

radiation group compared to untreated cells. Analysis of NANOGP8

showed no signicant dierences. Additionally, the treated cells showed

an altered, partially stronger secretion of the cytokines IL6 and IL8.

Conclusions: Irradiation aects the proliferation of meningioma cells in

dierent ways and can induce the formation of spheroids in low-dose irra-

diated cultures. In addition, photon exposure leads to a signicantly high-

er expression of embryonic and stem cell associated NANOG1. erefore,

ionizing radiation seems to be a potential factor in cell reprogramming

and thus in tumor development.

Disclosure Statement: e authors report no conicts of interest.

689

Hepatocyte-Specific Deletion of mTOR Accelerates Colorectal

Liver Metastasis

Long Jiao 1; Roman Eickho 2; Athanassios Fragoulis 2; Ulf Peter Neumann 2;

Thorsten Cramer 2

1Surgery, RWTH University Aachen, Aachen, Deutschland

2RWTH Aachen University Hospital, RWTH University Aachen, Aachen,

Deutschland

Purpose: e mTOR protein is of central importance for the regulation

of cell proliferation, metabolism and autophagy. Activation of the mTOR

pathway is frequently found in cancer, resulting in the notion that tar-

geting mTOR represents a useful approach for cancer therapy. Of note,

mTOR inhibitors have thus far failed to demonstrate signicant antipro-

liferative ecacy in the majority of cancer types. It is therefore of pivot-

al importance to better understand the functional signicance of mTOR

inhibition for the pathogenesis of cancer. We sought to characterize the

cell type-specic role of mTOR for the pathogenesis of colorectal liver

metastases.

Methods: We established a liver epithelial cell (LEC)-specic knock-out

(KO) of mTOR via the Cre/loxP-system (termed mTORLEC mice) and char-

acterized the growth of colorectal liver metastases (CRLM) in mTORLEC

mice compared to wildtype (WT) controls.

Results: Unexpectedly, tumor nodules in the CRLM model were signi-

cantly larger in mTORLEC mice compared to controls. We hypothesized

that the KO of mTOR in LECs resulted in the formation of a pro-tum-

origenic microenvironment in the liver. To further analyze this, we de-

termined the expression of pro-inammatory factors in WT versus KO

livers. While the expression of COX-2, HIF-1α, TNF-α and IL-6 was not

aected, IL-1β gene expression was found to be signicantly higher in the

livers of mTORLEC mice. Furthermore, mTORLEC mice displayed peripor-

tal leukocyte accumulation that was absent in livers from WT mice. e

functional relevance of this nding for the accelerated metastasis forma-

tion in mTORLEC mice is currently being evaluated by us.

Conclusions: We show an unexpected acceleration of liver metastases

upon functional deletion of mTOR specically in liver epithelial cells.

Our results add a further layer of complexity to the biology of mTOR and

suggest that cell and tissue type-specic factors need to be considered in

order to comprehend the role of mTOR for tumor biology.

Disclosure Statement: none

757

PGRMC1 Alters de Novo Lipid Biosynthesis Resulting

in Enhanced Oncogenic Signaling

Nadia Stamm 1; Hannah Asperger 1; Marina Ludescher 1; Tanja Fehm 1;

Hans Neubauer 2

1Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf,

Forschungslabor, Düsseldorf, Deutschland

2Klinik für Geburtshilfe und Frauenheilkunde, Universitätsklinikum Düsseldorf,

Düsseldorf, Deutschland

Purpose: Progesterone Receptor Membrane Component-1 (PGRMC1) is

upregulated in breast cancers and is associated with a worse survival in

breast cancer patients. In the present study we describe a potential mecha-

nism by which PGRMC1 potentially contributes to breast cancer progres-

sion through deregulation of cholesterol and lipid homeostasis, leading to

enhanced oncogenic signaling.

Methods: PGRMC1 interaction partners were identied by co-immuno-

precipitation followed by mass spectrometry and validated using proxim-

ity ligation assay (PLA) in various breast cancer cell lines. To study how

elevated PGRMC1 expression contributes to cholesterol homeostasis, we

determined levels of cholesterol and estradiol in PGRMC1 overexpressing

breast cancer cells and investigated sensitivity to statin treatment. Addi-

tionally, we determined the activity of estrogen receptor (ERα) at condi-

tions of PGRMC1 overexpression and downregulation.

Results: PGRMC1 overexpression resulted in increased proliferation rates

in cell culture and in signicantly increased tumor volume in xenogra

models. PGRMC1 was further found to interact with proteins involved

in cholesterol and lipid synthesis. Overexpression of PGRMC1 resulted

in increased cholesterol- and estradiol levels, indicating a contribution

of PGRMC1 to cholesterol homeostasis. Interestingly, PGRMC1 overex-

pressing cells established a higher sensitivity to statin treatment, indicat-

ing an increased dependence on cholesterol biosynthesis pathway in these

cells. Finally, a positive correlation between PGRMC1 and ERα expression

levels and -activation was identied, suggesting the activation of ERα sig-

naling by cholesterol metabolites.

Conclusions: PGRMC1 is potentially involved in cholesterol homeosta-

sis by modulation of enzymes of the respective biosynthesis pathway re-

sulting in elevated levels of cholesterol and its metabolites. Subsequent

activation of oncogenic signaling cascades could contribute to breast

cancer progression. erefore PGRMC1 represents a potential target for

anti-cancer therapy.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts6

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2018

Index

2018

859

Serum- Cytokine Prole after Extended Liver Resection

Sandra Brückner 1; Laura Henneke 1; Michael Bartels 2;

Philipp Felgendre 3, 4; Uta Dahmen 4; Utz Settmacher 4;

Bruno Christ 1; Hans-Michael Tautenhahn 3, 4

1Clinics of Visceral, Transplantation, Thoracic and Vascular Surgery, University

Hospital Leipzig, Leipzig, Deutschland

2Clinics of General and Visceral Surgery, HELIOS Park-Klinikum Leipzig, Leipzig,

Deutschland

3Research Programme “Else Kröner-Forschungskolleg AntiAge”, University

Hospital Jena, Jena, Deutschland

4Clinics of General, Visceral and Vascular Surgery, University Hospital Jena, Jena,

Deutschland

Purpose: An extended partial hepatectomy (ePHx) is oen the only cura-

tive option for patients suering from primary or secondary liver tumors.

e substantial loss of liver parenchyma may lead to organ dysfunction

respectively liver failure. e molecular ways, which are accompanied by

liver failure, are not known in detail yet. For this reason this study should

show the change of cytokine proles aer liver resection.

Methods: In this study 100 cytokines in the serum of patients, undergoing

an ePHx (>70%) in cause of liver tumor, were determine. e cytokines

were quantied 24h before and aer liver resection with the Proteome

ProlerTMHuman Cytokine Array Kit (R&D systems).

Results: 14 out of 100 dened cytokines shows a signicantly higher level

24h aer liver resection compared to preoperative status. MIF (Macro-

phage migration inhibitory factor) and ST2 (Interleukin 1 receptor-like

1; Receptor for interleukin-33) shows more than doubling in the level of

intensity. Also Lipocalin-2, MMP9 (Matrix metallopeptidase 9), PDG-

FAA (Platelet-derived growth factor alpha polypeptide) and TFF3 (Trefoil

factor 3) were inuenced by the extended liver resection. e signicantly

inuenced cytokines were analyzed by the STRING database, resulting

in a calculation of the aected KEGG pathways. is calculation clearly

shows an eect of the liver resection on the TNF signaling pathway (path-

way ID: 04668) (p=0.00542) and the immune system process (pathway ID:

0002376) (p=9.52e-6).

Conclusions: Due to liver resection, a number of dierent immunological

processes will be inuenced. Based on this study the TNF signaling path-

way seems to be one of the main important processes in liver regenera-

tion in our mind. Identifying such pathways and detecting there inuence

in liver regeneration forms the foundation of developing new molecular

targets which will open up new therapeutic approaches supporting the

post-operative liver regeneration.

Disclosure Statement: nothing to declare

Breast Cancer

Vorträge

629

Impact of Chemotherapy-Induced Ovarian Failure (CIOF) on

Disease-Free Survival (DFS) and Overall Survival (OS) in Young

Women with Early Breast Cancer (EBC)

Jenny Furlanetto 1; Valentina Nekljudova 1; Andreas Schneeweiss 2;

Christian Thode 3; Carsten Denkert 4; Michael Untch 5; Martina Bassy 3;

Thomas Karn 6; Peter A. Fasching 7; Elmar Stickeler 8; Christian Schem 9;

Frederik Marmé 10; Eva-Maria Grischke 11; Marion van Mackelenbergh 12;

Dominika Strik 13; Sabine Schmatloch 14; Volkmar Müller 15; Sibylle Loibl 1

1GBG, Neu-Isenburg, Germany

2Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany

3Amedes MVZ wagnerstibbe für Laboratoriumsmedizin, medizinische

Mikrobiologie und Immunologie, Göttingen, Göttingen, Germany

4Institut für Pathologie Philipps-Universität Marburg, Marburg, Germany

5Helios Kliniken Berlin-Buch, Berlin, Germany

6Universitätsklinikum Frankfurt, Frankfurt, Germany

7University Hospital Erlangen, Erlangen, Germany

8Uniklinik RWTH Aachen, Aachen, Germany

9Mammazentrum Hamburg, Hamburg, Germany

10Universitätsfrauenklinik Mannheim, Mannheim, Germany

11Universitätsklinikum Tübingen, Tübingen, Germany

12Universitätsklinikum Schleswig-Holstein, Klinik für Gynäkologie und

Geburtshilfe, Schleswig-Holstein, Kiel, Germany

13Endokrinologikum Berlin, Berlin, Germany

14Elisabeth Krankenhaus Kassel, Kassel, Germany

15Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Purpose: Previous data has shown that chemotherapy (CT)-induced

amenorrhea was associated with a better DFS and OS in premenopausal

patients (pts) with EBC, regardless of the hormone receptor status.

Methods: 740 pts aged ≤45yrs treated with anthracycline/taxane (A/T)-

based CT for EBC from 4 German neo-/adjuvant trials were examined.

Centrally assessed estradiol (E2) and follicle-stimulating hormone (FSH)

in blood samples were collected at baseline and 4 wks aer the last

chemotherapy administration. CIOF was dened as E2 <52.2 ng/L and

FSH >12.4IU/L aer CT for pts with premenopausal hormone levels at

baseline (n=696). We present 4-year DFS and OS overall and in subgroups

by hormone receptor status and age.

Results: Median follow-up was 49.6 [48.8-50.3] months. Overall DFS: in

all pts without CIOF vs CIOF 65.2% vs 84.0%, p<0.001 (hazard ratio [HR]

2.06, 95%CI 1.36-3.12); in HR+ pts (n=395) 61.8% vs 87.5%, <0.001 (HR

2.69, 95%CI 1.57-4.60); in HR- pts (n=301) 71.6% vs 79.6%, p=0.266 (HR

1.47, 95%CI 0.74-2.89); in pts <30 yrs (n=60) 68.3% vs 92.6%, p=0.026

(HR 4.87, 95%CI 1.05-22.63); in pts 30-34 yrs (n=99) 59.9% vs 80.1%,

p=0.108 (HR 1.99, 95%CI 0.85-4.68); in pts 35-39 (n=200) yrs 63.5% vs

81.9%, p=0.116 (HR 1.85, 95%CI 0.85-4.04); in pts ≥40 yrs (n=337) 69.3%

vs 85.2%, p=0.565 (HR 1.41, 95%CI 0.44-4.51). OS in pts without CIOF

vs CIOF was 89.5% vs 92.7%, p=0.272 (HR 1.46, 95%CI 0.74-2.90); within

subgroups a trend towards a better OS was seen only in HR+ pts: 88.4% vs

95.9%, p=0.035 (HR 0.49, 95%CI 1.04-5.99).

Discussion: Our results support that pts with CIOF aer CT for EBC had

a better DFS compared to pts without CIOF, in particular if very young.

Moreover, we show that in HR+ BC, CIOF was associated with a signi-

cant improvement of DFS and OS.

Conclusions: Pts with CIOF aer A/T-based CT for EBC show a better

DFS, especially if <30 yrs or HR+. is DFS improvement translates in an

OS advantage in the latter group.

Reference:

1. Swain et al. NEJM 2010

Disclosure Statement: e study was supported by Walter Schulz Stiung.

AS reported grants from Celgene, Roche, AbbVie, Molecular Partner; personal

fees from Roche, AstraZeneca, Celgene, Pzer, Novartis, MSD, Tesaro, Lilly. VM

reported personal fees from Amgen, AstraZeneca, Diichi-Sankyo, Eisai, Pzer

Novartis, Roche, Celgene, Teva, Janssen-Cilag, Genomic Health, Hexal, Pierre

Fabre, MSD, Lilly, Tesaro, Nektar and grants from Novartis, Roche, Seattle Genet-

ics. PAF reported grants from Novartis, Biontech, Cepheid and personal fees from

Novartis, Roche, Pzer, Celgene, Daiichi-Sankyo, Teva, Astra Zeneca, Merck Sharp

& Dohme, Myelo erapeutics, Macrogenics, Eisai, Puma. MvM reported personal

fees from AstraZeneca, Novartis, Amgen.

e other co-authors had nothing to disclose.

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Index

2018

Poster

114

Gibt es einen Zusammenhang zwischen Silikonimplantaten

und dem Anaplastisch-Großzelligem Lymphom?

Lukas Prantl 1; Britta Kühlmann 1; Uwe Von Fritschen 2

1Hochschulzentrum für Plastische Chirurgie, Universität Regensburg

2Plastische Chirurgie, Berlin

Purpose: Über 80% der Brustrekonstruktionen werden weltweit mit Im-

plantaten durchgeführt. Die Sicherheit dieser Medizinprodukte und vor

allem der Zusammenhang der Bildung eines sehr seltenen Tumors des

lymphatischen Systems, das Breast Implant Associated Anaplastic Large

Cell Lymphoma (BIA-ALCL) sowie die Entstehung eines unklaren Symp-

tomenkomplexes, dem Autoimmune/Inammatory Syndrome Induced

by Adjuvants (ASIA) werden diskutiert.

Die Inzidenz des BIA-ALCL wird in der Literatur sehr unterschiedlich

angegeben. Dies liegt an uneinheitlich verwendeten Klassikationssyste-

men, unstrukturierten Datensammlung, möglichen Doppelmeldungen

in die Register, unsicheren klinischen und pathologischen Angaben und

fehlenden Daten zur Anzahl implantierter Implantate als Denominator. In

Deutschland sind bisher zwölf Fälle gemeldet.

Methods: Anhand der im Tumorzentrum Regensburg erhobenen Daten

über 17 Jahren errechneten wir die Inzidenz des CD-30 positiven und

ALK negativen Lymphoms.

Results: Von 170.293 erfassten Tumoren bei einer Population von 2.1 Mil-

lionen waren zwölf Fälle CD30 positiv und ALK negativ. In keinem Fall

war der Tumor mit einem Burstimplantat assoziiert.

Conclusions: Anhand von Hochrechnungen können wir eine Inzidenz

des BIA-ALCL von 4 auf 1.000.000 Implantat Jahre angeben. Infolge han-

delt es sich bei dem BIA-ALCL um eine äußerst seltene Komplikation von

Silikonimplantaten.

Disclosure Statement: keine

119

Neratinib + Capecitabine Versus Lapatinib + Capecitabine

in Patients with HER2+ Metastatic Breast Cancer Previously

Treated with ≥ 2 HER2-Directed Regimens: The Multinational,

Randomized, Phase III Trial Nala

Cristina Saura 1; Thomas Decker 2; Urs Breitenstein 3; Andreas Müller 4;

Marianne Just 5; Jens Huober 6; Christian Schem 7; Marina Wirtz 8;

Bernhard Heinrich 9; Daniel Egle 10; Alexandre Bodmer 11;

Maximilian Borner 12; Serban Dan Costa 13; Adam Brufsky 14;

Nala Investigators 15

1Vall d’Hebron University Hospital, Barcelona, Spanien

2Gemeinschaftspraxis fuer Haematologie und Onkologie GbR, Ravensburg,

Deutschland

3Onkotentrum Zurich 04, Zurich, Schweiz

4Breast Unit, Kantonsspital Winterthur, Winterthur, Schweiz

5Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland

6Universitaetsklinikum Ulm, Brustzentrum, Ulm, Deutschland

7Mammazentrum Hamburg, Hamburg, Deutschland

8SAH Eschweiler, Eschweiler, Deutschland

9Haematologisch-onkologische Praxis, Augsburg, Deutschland

10Medizinische Universitaet Innsbruck, Innsbruck, Österreich

11Hôpitaux Universitaires de Genève, Geneva, Schweiz

12Brustzentrum Bern, Bern, Schweiz

13Otto-von-Guericke University Magdeburg, Magdeburg, Deutschland

14Magee-Womens Hospital of UPMC, Pittsburgh, PA, United States

Purpose: NALA (NCT01808573) is a multinational, randomized, open-la-

bel, phase III trial of neratinib (an irreversible pan-HER tyrosine kinase in-

hibitor [TKI]) + capecitabine (N+C) vs lapatinib (a reversible dual TKI) +

C (L+C) in patients with stage IV HER2+ metastatic breast cancer (MBC)

who had received ≥ 2 prior HER2-directed regimens for MBC.

Methods: Patients were randomized 1:1 to N (240 mg qd po) + C (750

mg/m2 bid po) or L (1250 mg qd po) + C (1000 mg/m2 bid po). Patients

on N had mandatory diarrhea prophylaxis. Co-primary endpoints were

centrally assessed progression-free survival (PFS) and overall survival

(OS). Secondary endpoints were objective response rate (ORR); duration

of response (DoR); clinical benet rate (CBR); time to intervention for

symptomatic metastatic central nervous system (CNS) disease; safety.

Results: 621 patients were randomized (307 to N+C; 314 to L+C). PFS

was improved with N+C vs L+C (HR = 0.76; 95% CI 0.63–0.93; p = 0.006);

6-month PFS rates were 47.2% vs 37.8% for N+C vs L+C, respectively. OS

rates at 12 months were 72.5% vs 66.7% (HR = 0.88; 95% CI 0.72–1.07;

p = 0.2086). ORR in patients with measurable disease was 32.8% with

N+C vs 26.7% with L+C (p = 0.1201) with longer DoR for N+C (HR =

0.50; 95% CI 0.33–0.74; p = 0.0004). CBR for N+C was 44.5% vs 35.6% for

L+C (p = 0.0328). Time to intervention for symptomatic CNS disease was

delayed with N+C vs L+C (overall cumulative incidence 22.8% vs 29.2%;

p = 0.043). Treatment-emergent adverse events (TEAEs) were similar be-

tween arms. G3 diarrhea was more frequent with N+C (24.4% vs 12.5%

for L+C) but with similar median duration (4 d). TEAE-related discontin-

uation rates were lower for N (10.9%) than for L (14.5%).

Conclusions: N+C signicantly improved PFS with a trend towards

improved OS vs L+C. N+C resulted in a reduced incidence of interventions

for CNS progression compared to L+C. No new safety signals were

observed.

e study was published at the ASCO Annual Meeting 2019.

142

Germline Mutation Status and Therapy Response in

High-Risk Early-Stage Breast Cancer: a Secondary Analysis

of the Geparocto Randomized Clinical Trial (NCT02125344)

Esther Pohl-Rescigno 1; Jan Hauke 1; Kerstin Rhiem 1; Volker Möbus 2;

Jenny Furlanetto 3; Carsten Denkert 4; Peter A. Fasching 5; Claus Hanusch 6;

Hans Tesch 7; Nana Weber-Lassalle 1; Volkmar Müller 8; Michael Untch 9;

Kristina Lübbe 10; Bianca Lederer 3; Christian Jackisch 11;

Valentina Nekljudova 3; Rita K. Schmutzler 1; Sibylle Loibl 3;

Andreas Schneeweiss 12; Eric Hahnen 1

1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology

(CIO), University of Cologne, Faculty of Medicine and University Hospital

Cologne, Cologne, Deutschland

2Department of Gynecology and Obstetrics, Klinikum Frankfurt Höchst,

Academic Hospital of the Goethe University Frankfurt, Frankfurt, Deutschland

3German Breast Group (GBG), Neu-Isenburg, Deutschland

4Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum

Marburg, Marburg, Deutschland

5University Hospital Erlangen, Erlangen, Deutschland

6Rotkreuzklinikum, Frauenklinik, Munich, Deutschland

7Hämatologisch-Onkologische Gemeinschaftspraxis, Frankfurt, Deutschland

8Department of Gynecology, Hamburg-Eppendorf University Medical Center,

Hamburg, Deutschland

9Department of Gynecology and Obstetrics, Helios Klinikum Berlin-Buch, Berlin,

Deutschland

10Diakovere Henriettenstift, Breast Center, Hannover, Deutschland

11Sana Klinikum Oenbach GmbH, Oenbach, Deutschland

12National Center for Tumor Diseases, University of Heidelberg, Heidelberg,

Deutschland

Purpose: GeparOcto compared the ecacy of two neoadjuvant treatment

regimen in high-risk early breast cancer (BC): Sequential intense dose-

dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly

paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carbo-

platin (PMCb) in triple-negative BC (TNBC). ere was no dierence

in pathological complete response (pCR) rates (Schneeweiss et al. Eur J

Cancer. 2019;106:181-192).

Methods: Germline mutation analysis of BRCA1/2 and 16 further BC

predisposition genes using blood-derived DNA from 914 female patients

(pts) enrolled (393 pts with TNBC, 156 pts with HER2-/HR+ BC; and 365

pts with HER2+ BC). pCR rates (ypT0/is ypN0 denition) were stratied

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2018

according to the germline (g) mutation status overall, by treatment arm,

and tumor subtype.

Results: 96 of the 914 pts (10.5%) carried gBRCA1/2 mutations and

achieved higher pCR rates than pts without gBRCA1/2 mutations (60.4%

vs 46.7%, OR:1.74, P=.012). e gBRCA1/2 mutation prevalence was 17.6%

in TNBC, 14.1% in HER2-/HR+ BC, and only 1.4% in HER2+ BC. Irre-

spective of the treatment arm, pts with TNBC and gBRCA1/2 mutations

showed higher pCR rates compared with TNBC pts without gBRCA1/2

mutations (69.6% vs 46.0%, OR:2.69, P=.001). A positive gBRCA1/2 mu-

tation status predicts therapy response in both, the PMCb arm (74.3% vs

47.0%, OR:3.26, P=.005) and the iddEPC arm (64.7% vs 45.0%, OR:2.24,

P=.040); dierences between treatment arms did not reach levels of signif-

icance (P=.389). In the subgroup of pts with HER2-/HR+ BC, a positive

gBRCA1/2 mutation status predicts signicantly higher pCR rates (31.8%

vs 11.9%, OR:3.44, P=.020).

Conclusions: Eective chemotherapy for gBRCA1/2-mutated TNBC

is commonly suggested platinum-based. With a pCR rate of 64.7%, we

demonstrate that iddEPC appears to be similar eective in these pts. Of

interest is the signicantly higher pCR rate in HER2-/HR+ gBRCA1/2 car-

riers compared to non-carriers. e question arises whether all pts with

high-risk luminal BC should be oered gBRCA1/2 testing prior to treat-

ment start.

150

Factors Inuencing the Time to Surgery after Neoadjuvant

Chemotherapy in Breast Cancer Patients

Carolin Müller 1; Stephanie Juhasz-Böss 2; Gilda Schmidt 2;

Peter Jungmann 2; Erich-Franz Solomayer 2; Georg-Peter Breitbach 2;

Ingolf Juhasz-Böss 2

1Universitätsklinikum des Saarlandes, Gynäkologie, Geburtshilfe und

Reproduktionsmedizin, Homburg, Deutschland

2Universitätsklinikum des Saarlandes

Purpose: It is suspected, that delayed surgery aer neoadjuvant chemo-

therapy leads to a worse outcome in breast cancer patients. We therefore

determined time interval between the end of neoadjuvant chemotherapy

(NACT) and surgery, as well as possible inuencing factors.

Methods: All patients receiving NACT due to newly diagnosed breast

cancer from 2015 to 2017 at Department of Gynecology, Saarland Uni-

versity Medical School, were included. e time interval between end of

NACT and surgery was dened as primary endpoint. Possible delaying

factors were investigated: Age, study participation, outpatient and inpa-

tient presentations, implants/expander, MRI preoperatively, discontinua-

tion of chemotherapy, genetic mutations.

Results: Data of 139 patients was analyzed. e average age was 53 years

(+/- 13). e time interval between end of NACT and surgery was 28 days

(±9). Clinical presentations on outpatient and inpatient basis showed a

statistically signicant prolonging eect on the time between NACT and

surgery (p=0.002; p<0.001). Also, discontinuation of NACT led to a pro-

longed time to surgery (p=0.005). In contrast, a proven genetic mutation

shortened the time to surgery (p<0.001).

Conclusions: Every outpatient presentation prolonged the time to sur-

gery by an average of two days, inpatient presentations prolonged the time

to surgery by an average of seven days. Discontinuation of NACT delayed

surgery by an average of six days. Patients with proven genetic mutation

had surgery seven days earlier. Patients age, participation in clinical stud-

ies, oncoplastic surgery and preoperative MRI scans did not delay therapy

onset.

152

The Potential of Claims Data for Long-Term Follow-Up

of Breast Cancer Patients in Germany

Miriam Heinig 1; Ulrike Haug 1, 2

1Leibniz-Institut für Präventionsforschung und Epidemiologie – BIPS GmbH,

Bremen, Deutschland

2Universität Bremen, Fakultät Human- und Gesundheitswissenschaften,

Bremen, Deutschland

Purpose: Population-based data on long-term treatment patterns and

clinical outcomes in cancer patients are important but hardly available

from German cancer registries. Exemplied by breast cancer (BC) pa-

tients, we aimed to explore the potential of German claims data for pro-

viding long-term follow-up information on cancer patients.

Methods: We used the German Pharmacoepidemiological Research Da-

tabase (GePaRD) containing claims data from four statutory health in-

surances with information on ~25 million persons. Based on previously

developed algorithms using ICD-10 codes, we identied patients newly

diagnosed with BC in 2008 and classied them into three groups: no af-

fected lymph nodes/metastasis (noNM), aected lymph nodes only (on-

lyN) or distant metastasis (M) at diagnosis. e cohort was followed up

until end of 2016 or death. We characterized the groups regarding initial

and subsequent therapies (surgery, medical therapy and radiotherapy),

metastases and deaths occurring during follow-up.

Results: Aer exclusion of patients switching health insurance during

follow-up (9% of the initial cohort) we included 11,717 BC patients diag-

nosed in 2008 (noNM: 82%, onlyN: 12%, M: 7%) with a mean age of 63

years (median follow-up: 8.4 years). During the observation period, 11%

of the cohort received no breast surgery (group M: 21%), 28% received

more than one surgery (second surgery in rst year: 81%; later: 19%) and

29% had a mastectomy (in rst year: 91%, only later: 9%). Of the total

cohort, 8% received neoadjuvant therapy, 7% ever received monoclonal

antibodies, 52% never received chemotherapy (group noNM: 92%) and

28% never received radiotherapy. Overall, 25% of the cohort died (group

M: 22%).

Conclusions: Claims data provide valuable information on the long-term

course and treatment of cancer patients, avoiding substantial loss-to-fol-

low-up and incomplete reporting of therapies. Combining claims data

with cancer registry data containing detailed tumor information may cre-

ate synergies that should be explored.

Disclosure Statement: None.

153

HER4 Expression in Estrogen Receptor-Positive Breast

Cancer is Associated with Decreased Sensitivity to Tamoxifen

Treatment and Reduced Overall Survival of Postmenopausal

Women

Gero Brockho 1; Dominik Chittka 2; Stefan Buchholz 3;

Simone Diermeier-Daucher 3; Monika Klinkhammer-Schalke 4;

Florian Zeman 5; Anja-Kathrin Wege 1; Olaf Ortmann 1

1Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg,

Deutschland

2Klinik für Innere Medizin II, Universität Regensburg, Deutschland

3Klinik für Frauenheilkunde und Geburtshilfe, Universität Regensburg,

Regensburg, Deutschland

4Institut für Qualitätssicherung Versorgungsforschung, Tumorzentrum,

Universität Regensburg, Deutschland

5Zentrum für Klinische Studien, Universität Regensburg, Deutschland

Purpose: e sensitivity of estrogen receptor positive breast cancers to

tamoxifen treatment varies considerably and the molecular mechanisms

aecting the response rates are manifold. e human epidermal growth

factor receptor related receptor HER2 is known to trigger intracellular sig-

naling cascades that modulate the activity of coregulators of the estrogen

receptor which in turn reduces the cell sensitivity to tamoxifen treatment.

However, the impact of HER2 related receptor tyrosine kinases HER1,

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2018

Index

2018

HER3, and in particular HER4 on an endocrine treatment eciency is

largely unknown.

Methods: Here we retrospectively evaluated the importance of HER4

expression on the outcome of tamoxifen and aromatase inhibitor treated

estrogen receptor positive breast cancer patients (n = 258) – either pre- or

postmenopausal. In addition, we experimentally analyzed the eciency of

tamoxifen treatment as a function of HER4 coexpression in-vitro.

Results: We found a signicantly improved survival of tamoxifen treated

postmenopausal breast cancer patients in the absence of HER4 compared

to those with pronounced HER4 expression. In accordance with this nd-

ing the sensitivity to tamoxifen treatment of estrogen and HER4 recep-

tor positive ZR-75-1 breast cancer cells can be signicantly enhanced by

HER4 knockdown.

Conclusions: We suggest an HER4 / estrogen receptor interaction that

impedes tamoxifen binding to the estrogen receptor and reduces treat-

ment eciency. Whether the sensitivity to tamoxifen treatment can be

enhanced by an anti-HER4 targeting needs to be prospectively evaluated.

Reference:

1. Brockho G. Target HER four in breast cancer? Oncotarget. 2019 May

7;10(34):3147-3150.

[…] Brockho G. HER4 expression in estrogen receptor-positive breast cancer

is associated with decreased sensitivity to tamoxifen treatment and reduced

overall survival of postmenopausal women. Breast Cancer Res. 2018 Nov

20;20(1):139.

Disclosure Statement: e authors declare no conicts of interest.

160

Capivasertib (AZD5363) Plus Fulvestrant Versus Placebo Plus

Fulvestrant After Relapse or Progression on an Aromatase

Inhibitor in Metastatic ER-Positive Breast Cancer (Faktion): a

Randomized, Double-Blind, Placebo-Controlled, Phase II Trial

Joke Tio 1; Artur Kokornaczyk 2; Björn Tschalener 2; Rober Hugh Jones 3

1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster,

Münster, Deutschland

2AstraZeneca GmbH, Wedel, Deutschland

3Velindre Cancer Centre, Velindre Cancer Centre, Cardi, United Kingdom

Purpose: e PI3K/AKT signaling pathway is frequently activated in pa-

tients (pts) with estrogen receptor (ER) positive breast cancer (ER+BC)

and has been implicated in endocrine therapy resistance. Capivasert-

ib (Capi) is a highly-selective, oral, small molecule AKT inhibitor. e

FAKTION trial investigated the addition of Capi to fulvestrant (Ful) for

postmenopausal women with ER+ and HER2- BC aer relapse or disease

progression on an aromatase inhibitor (AI).

Methods: FAKTION is an investigator-led, double-blind, placebo-con-

trolled, randomised phase II trial. Patients were recruited from 21 UK

sites and randomly assigned (1:1) to Ful 500mg (day 1 and 15 of cycle 1

and day 1 only of subsequent 28 day cycles) with either Capi 400mg bd or

placebo (4 days on/3 days o starting C1D15) until disease progression,

unacceptable toxicity or withdrawal of consent. Allocation was balanced

by minimisation according to PIK3CA mutation and PTEN expression

status, measurable/non-measurable disease, and primary/secondary en-

docrine resistance. e primary endpoint was PFS. e trial had 90%

power to detect a hazard ratio of 0.65 at the one-sided 20% signicance

level. Secondary endpoints included OS, ORR and clinical benet rates,

safety and the eect of PI3K/AKT pathway activation on PFS.

Results: Between Mar 2015 and Mar 2018, 140 pts were randomised to

Ful + Capi (n = 69) or Ful + placebo (n = 71). In the ITT analysis, aer 112

events, mPFS was 10.3 months (m) for Capi compared to 4.8m for placebo

(HR 0.57; 95% CI: 0.39 to 0.84; one-sided p = 0.0017; two-sided 0.0035).

Fiy-two deaths were reported. Median OS was 26.0m for Capi compared

to 20.0m for placebo, with a survival dierence starting to emerge aer

12m (HR = 0.59; 95% CI: 0.34 to 1.05; two-sided p = 0.071).

Conclusions: e trial met its primary endpoint. Addition of Capi to Ful

for patients with endocrine resistant advanced breast cancer resulted in

signicantly longer PFS and an improvement in OS. Results warrant fur-

ther investigation of Capi for the treatment of ER positive breast cancer.

162

Identication of a Novel Gene Disrupting Germline Mutation

Derived from L1PA7 Transposition Into The BRCA2 Coding

Sequence: Further Improvement of the Trurisk® Gene Panel

Analysis

Esther Pohl-Rescigno; Corinna Ernst; Jan Hauke; Gizem Sahin;

Lisa Richters; Julia Driesen; Mohamad Kayali;

Barbara Wappenschmidt; Rita K. Schmutzler; Eric Hahnen

Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology

(CIO), University of Cologne, Faculty of Medicine and University Hospital

Cologne, Cologne, Deutschland

Purpose: Although the sensitivity of molecular geneticdiagnostics has

been improved by next generation sequencing (NGS) applications, no

causal mutations can be identied in many high-risk breast and ovari-

an cancer(BC/OC) families. One possible reason is the existence of yet

unknown genetic risk factors; another explanation is the limitation of

NGS analyses e.g. the identication of large insertions (Qian et al. Cancer

Genet. 2017). By re-analyzing NGS data, we focused on identifying gene

disruptions by large insertions of mobile genetic elements.

Methods: An in-house approach was employed to scan BWA (Bur-

rows-Wheeler Aligner)-MEM (maximal exact matches) algorithm-pro-

duced read mappings of 4,218 BC/OC index patients for accumulations

of break points in split-read alignments (Li 2013. arXiv:1303.3997). We

performed long-range polymerase chain reaction (PCR) by using primers

anking the predicted insertion breakpoint c.3258_3259 in BRCA2, sub-

sequent Sanger sequencing of gel-extracted PCR products, and sequence

analysis of the insertion using RepeatMasker.

Results: We were able to identify a novel insertion c.3258_3259insL1 in

BRCA2 which is predicted to cause a frameshi and premature protein

truncation p.(Ile1086Metfs*54) resulting in the loss of 2,280 amino ac-

ids. erefore, loss of BRCA2 function is very likely and the variant can

be classied as pathogenic (IARC class 5). e insertion derives from the

transposition of ~400 bp of the 3´-end of human retrotransposon LINE-1

(L1Hs), also known as L1PA7, into the BRCA2 coding sequence.

Conclusions: Re-analyzing NGS data from 4,218 BC/OC index cases, we

identied the novel BRCA2-disrupting insertion c.3258_3259insL1 in a

female patient with bilateral BC (age at rst diagnosis 30 and 36 years). Al-

though only identied once, this study underlines the need for continuous

improvement of bioinformatic NGS data analysis. Detection of unusual

pathogenic variants further improves the sensitivity of routine diagnostics

in order to provide the best possible counselling and risk calculation to

those seeking advice.

167

Clinical Signicance of PIK3CA and ESR1 Mutations in CTDNA

and FFPE Samples from The Monarch2 Study of Abemaciclib

Plus Fulvestrant

Eva Maria Grischke 1; Sara Tolaney 2; Masakazu Toi 3; Patrick Neven 4;

Joo Hyuk Sohn 5; Antonio Llombart-Cussac 6; Hatem Soliman 7;

Lacey Litcheld 8; Sameera Wijayawardana 8; Tammy D Forrester 8;

Valerie Jansen 8; George W Sledge 9

1Tübingen, Universität Tünbingen, Tübingen, Deutschland

2Boston, Harvard University, Boston, United States

3Kyōto, Kyoto University, Kyōto, Japan

4Löwen, Universitaire Ziekenhuizen Leuven, Löwen, Belgien

5Seoul, Yonsei Cancer Center, Seoul, Südkorea

6Valencia, Hospital Arnau Vilanova, Valencia, Spanien

7Tampa, Mott Cancer Center, Tampa, United States

8Indianapolis, Eli Lilly and Company, Indianapolis, United States

9Stanford, Stanford University, Stanford, United States

Purpose: We assessed clinical signicance of PIK3CA and ESR1 muta-

tions from patients treated with abemaciclib (A)+fulvestrant (F) and pla-

cebo (P)+F.

Methods: Baseline plasma samples (n=334) and FFPE tumor samples

(n=434) from 669 MONARCH2 patients were analyzed. Extracted DNA

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was analyzed by droplet digital PCR for 4 hotspot mutations of PIK3CA

(E542K; E545K; H1047L; H1047R) and ESR1 (D538G; Y537C; Y537N;

Y537S). Samples failing DNA QC or with mutation status undetermined

were excluded from analysis.

Results: PIK3CA mutations were detected in 40.3% of plasma and 39.9%

of FFPE samples. H1047R was the most frequent mutation. Concordance

of PIK3CA mutations in ctDNA and FFPE samples was 62.8%. ESR1

mutations were detected in 64.4% of plasma and 4.4% of FFPE samples.

D538G was the most frequent mutation. Concordance of ESR1 mutations

in ctDNA and FFPE samples was 37.1%; this is explained in part by the

biopsy site (primary vs metastatic). Co-mutations in PIK3CA and ESR1

were observed in 36.1% plasma and 1.5% FFPE samples. In PIK3CA wild-

type (WT) median PFS was 20 mo for A+F and 12.7 mo for P+F (HR:

0.68; 95%CI: 0.42, 1.09); PIK3CA mutant (M): median PFS=15 mo for

A+F and 5.7 mo for P+F (HR: 0.46; 95%CI: 0.27, 0.78); ESR1 WT: median

PFS=16.3 mo for A+F and 11.6 mo for P+F (HR: 0.69; 95%CI: 0.41, 1.18);

ESR1 M: median PFS=21.9 mo for A+F and 10.3 mo for P+F (HR: 0.49;

95%CI: 0.33, 0.73).

Conclusions: PIK3CA and ESR1 mutations in ctDNA correlated with

response to A. Addition of A to F improved PFS regardless of PIK3CA/

ESR1 status; however, magnitude of benet was numerically greater when

PIK3CA/ESR1 mutations were present.

168

A Phase 2 Study of Abemaciclib in Patients (PTS) with Brain

Metastases (BM) Secondary to HR+, HER2 Metastatic Breast

Cancer (MBC)

Carey Anders 1; Emily Le Rhun 3; Thomas Bachelot 4; Denise Yardley 5;

Ahmad Awada 6; Pierre Franco Conte 7; Peter Cabos 8; Melissa Bear 9;

Sarah Tolaney 10

1Durham, Duke Cancer Institute, Durham, United States

2München, Technische Universität München, München, Deutschland

3Lille, University Hospital, Lille, Frankreich

4Lyon, Centre Leon Berard, Lyon, Frankreich

5Nashville, Sarah Cannon Research Institute, Nashville, United States

6Brüssel, Institut Jules Bordet, Brüssel, Belgien

7Padua, University of Padova, Padua, Italien

8Denver, University of Denver, Denver, United States

9Indianapolis, Elli Lilly, Indianapolis, United States

10Boston, Dana-Farber Cancer Institute, Boston, United States

Purpose: Clinical data demonstrate that abemaciclib penetrates blood-

brain with comparable concentrations in tissues and plasma.

Methods: JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt

cohorts with BM secondary to HR+ MBC, non-small cell lung cancer,

or melanoma. We report on HR+, HER2- MBC pts. Eligible pts had ≥1

new or not previously irradiated measurable BM ≥10mm or a progressive

previously irradiated BM. Endocrine therapy (ET) was permitted to be

continued provided that extracranial disease was stable ≥3 months and

BM progression occurred on the ET. Abemaciclib was orally adminis-

tered 200mg BID. Primary endpoint was objective intracranial response

rate (OIRR; [complete response (CR)+partial response (PR)]) based on

Neuro-Oncology BM response assessment criteria. Secondary endpoints

were intracranial clinical benet rate, progression-free survival (PFS), and

safety.

Results: 58 pts were enrolled; 52 were evaluable. Pts had median of 4pri-

or systemic therapies, 75% had prior chemotherapy (0-6, median 2), 71%

had prior ET (0-4, median 1) in the metastatic setting. 50% pts had pri-

or whole-brain radiotherapy (RT), 39% stereotactic radiosurgery and 8%

surgical BM resection. Median time from RT to study enrollment was 9.4

months. Out of 52 evaluable pts, 3 had a conrmed intracranial response

(6% OIRR); 38% had a decrease in the sum of intracranial target lesions.

Intracranial clinical benet rate (CR+PR+stable disease persisting for ≥6

months) was 25%. Median PFS was 4.4 months (95%CI 2.6-5.5). Safety

and tolerability were similar to previous reports for abemaciclib.

Conclusions: Abemaciclib demonstrated intracranial clinical benet in

the study pts. Further evaluations are ongoing to identify MBC pts with

BM who might benet most from abemaciclib.

182

Breast Units – a Comparison of the Landscape in Germany

and the United Kingdom

Sandra Breitenbücher 1; Rüdiger Meierjürgen 2; Wilfried Boroch 2

1Stabsstelle Qualitätsmanagement und klinisches Risikomanagement,

Universitätsklinikum Essen, Essen, Deutschland

2FOM Hochschule für Oekonomie & Management, Essen, Deutschland

Purpose: Survival rates of Breast Cancer patients still dier in European

countries. Studies like the EUROCARE-5 study show a lower 5-year-sur-

vival-rate in Eastern Europe and the United Kingdom (UK)/Ireland com-

pared to the European average and Germany. 1 Here we select key per-

formance indicators (KPIs) with presumable impact on survival of Breast

Cancer patients and compare certication/inspection systems in Germa-

ny and the UK. We focus on the systems of OnkoZert (Germany), the

Care Quality Commission (CQC, England) and the European Society of

Mastology (EUSOMA). Utilization of certication systems like OnkoZert

and EUSOMA is voluntary, whereas the CQC keeps the care providers

under obligatory surveillance.

Methods: KPI selection resulted from literature analysis and an expert

survey. Experts were dened as people involved in Breast Cancer patient

care (i.e. physicians, nurses and people working in quality management or

certifying bodies). 78 experts were asked to ll in a short questionnaire.

e rate of return was 68%.

Results: Selected KPIs assumed to have a positive impact on the survival

rate of Breast Cancer patients were for example an early stage diagnosis, a

short interval between diagnosis and start of therapy, early access to new

therapies and a multidisciplinary collaboration of the treatment team.

Many of the selected KPIs were integrated into the requirements of the

analyzed certication/inspection systems. However, the level of detail and

frequency of inspection diered markedly.

Conclusions: Harmonization of certication systems on a European level

seems to be reasonable. More than 90% of the responding experts are con-

vinced that certication of Breast Units has a positive impact on care and

survival of Breast Cancer patients.

Reference:

1. Vgl. Sant, M. et al., Survival of women with cancers of breast and genital

organs in Europe 1999-2007[…] in: European Journal of Cancer, 2015, S. 2191

.; Allemani, C. et al.,Global surveillance of trends in cancer survival 2000-14

(CONCORD-3)[… ] in: e Lancet, 2018, S. 1023 .

Disclosure Statement: No disclosures.

184

Routine Care Reality of Patients with Metastatic Anti-Human

Epidermal Growth Factor Receptor 2 (HER2) Positive Breast

Cancer Who Received Treatment in Oncology Group Practices

in Germany Between 2012 and 2017

Rudolf Weide 1; Bernhard Rendenbach 2; Hans-Peter Laubenstein 2;

Ute Braun 3; Karl Hünermund 3; Oswald Burkhard 4; Peter Ehscheidt 5;

Stefan Feiten 6; Geothy Chakupurakal 1; Vera Friesenhahn 6;

Kristina Kleboth 6; Hubert Köppler 1; Julia Lutschkin 6; Jörg Thomalla 1;

Christoph van Roye 1; Jochen Heymanns 1

1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland

2Praxis für Hämatologie, Onkologie und Nephrologie, Trier, Deutschland

3Gemeinschaftspraxis für Hämatologie und Onkologie, Ludwigshafen,

Deutschland

4Internistische Gemeinschaftspraxis Hämatologie, Onkologie, Palliativmedizin,

Worms, Deutschland

5Onkologische Praxis Dr. Ehscheidt, Neuwied, Deutschland

6Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland

Purpose: Many treatment options have become available since the discov-

ery of an overexpression of HER2 in approximately 15–25% of all breast

cancer patients. Real world data concerning treatment sequences and out-

come from unselected patients who receive routine care are not known.

Methods: Retrospective analysis of all patients with metastatic HER2

positive breast cancer who were treated between 01/2012 and 12/2017 in

ve community-based oncology group practices in Germany. Data were

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extracted from patient les into a database and analyzed statistically using

SPSS.

Results: 146 female patients with a median age of 59.5 years (24–91) were

analyzed. 35% were in stage IV at diagnosis, 75% were hormone receptor

positive. Localizations of metastases were distributed as follows: 55% vis-

ceral, 17% bone, 5% CNS, 8% lymph nodes and 9% others. 1st line Anti

HER2 therapy consisted of trastuzumab+pertuzumab in 54%, trastuzum-

ab in 36%, lapatinib in 5% and trastuzumab emtansine in 4%. 2nd line

treatment was trastuzumab+pertuzumab in 63%, trastuzumab in 23%,

trastuzumab emtansine in 7%, lapatinib in 4% and trastuzumab+lapati-

nib in 2%. 3rd line therapy consisted of trastuzumab emtansine in 43%,

trastuzumab in 28%, trastuzumab+pertuzumab in 23% and lapatinib in

8%. Median overall survival (OS) was 54 months (1.1-69.4). OS was sig-

nicantly correlated with hormone receptor status. Patients with triple

positive tumors had a median OS of 56 months (3.8-69.4) compared to

33 months (1.1-62.1) in HER2 only positive patients (p=.004). OS depen-

dent strongly but not statistically signicant on the number of metastasis

localizations. Median OS of patients with 1 localization was 54.0 months

(1.1-69.4) compared to 40.8 months (2.1-56.4+) in patients with two or

more localizations.

Conclusions: OS improvements of patients with metastatic HER2 pos-

itive breast cancer are strongly restricted to hormone receptor positive

tumors most likely due to improved targeted therapies directed against

HER2 and the estrogen receptor.

Disclosure Statement: All authors report no conicts of interest

215

First Results of the Detect IVA Study –Everolimus Treatment

in Patients with HER2-Negative, Hormone-Receptor Positive

Metastatic Breast (MBC) Cancer and Circulating Tumor Cells

(CTC)

Thomas W. P. Friedl 1; Sabrina Krause 1; Peter Andreas Fasching 2;

Andreas Schneeweiss 3; Volkmar Müller 4; Sabine Riethdorf 5;

Florin-Andrei Taran 6; Fabienne Schochter 1; Arkadius Polasik 1;

Marie Tzschaschel 1; Amelie De Gregorio 1; Franziska Meier-Stiegen 7;

Jens Huober 1; Wolfgang Janni 1; Tanja Fehm 7

1Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm,

Deutschland

2Department of Gynecology and Obstetrics, University Hospital Erlangen,

Erlangen, Deutschland

3Department of Gynecology and Obstetrics, University of Heidelberg,

Heidelberg, Deutschland

4Department of Gynecology and Obstetrics, University Hospital Hamburg-

Eppendorf, Hamburg, Deutschland

5Department of Tumor Biology, University Hospital Hamburg-Eppendorf,

Hamburg, Deutschland

6Department of Gynecology and Obstetrics, University Hospital Tübingen,

Tübingen, Deutschland

7Department of Gynecology and Obstetrics, University Hospital Düsseldorf,

Düsseldorf, Deutschland

Purpose: e DETECT-IVa trial is a single-arm, open-label phase II study

for postmenopausal patients with HER2-negative, hormone-receptor pos-

itive MBC and HER2-negative CTCs. One of the main aims is to evaluate

the suitability of CTCs to provide both prognostic and predictive infor-

mation.

Methods: e DETECT IVa trial started in February 2014 and compris-

es two subsequent patient cohorts – the rst cohort received endocrine

therapy combined with the mTOR inhibitor everolimus, while the second

cohort of this ongoing trial receives endocrine therapy combined with the

CDK 4/6 inhibitor ribociclib. We performed an unplanned interim analy-

sis (data cuto July 2019) to obtain preliminary, rst results with regard to

patient characteristics, presence of CTCs 3 to 12 weeks aer study initia-

tion and overall survival (OS) for the rst (everolimus) cohort comprising

90 patients.

Results: Median age of the 90 patients of the everolimus cohort was 63

years (range 40 – 88 years). Median number of CTCs detected at baseline

was 5.5 (range 1 – 400 CTCs). At the time of data cuto, end of study treat-

ment was documented for 71 patients. 7 out of 8 patients that received

everolimus for the full study treatment period (12 months) had no CTCs

aer 3 to 12 weeks (no CTC data for one patient). 63 patients had to ter-

minate everolimus treatment prematurely because of death (6.3%), prog-

ress (58.7%), patients wish (11.1%), non-hematological toxicity (20.6%)

or treatment delays (3.2%). 23 (51.1%) out of 45 patients with premature

termination of everolimus treatment and available CTC data showed pres-

ence of CTCs aer 3 to 12 weeks. Median OS for 56 patients with data

available was 18.9 months (95% condence interval 11.8 – 26.0 months),

and presence of CTCs aer 3 to 12 weeks was signicantly associated with

poor OS (log rank test, p = 0.046).

Conclusions: Preliminary rst results of the DETECT-IVa trial indicate

that everolimus is still a valuable option for postmenopausal patients with

HER2-negative, hormone-receptor positive MBC. CTC detection pro-

vides prognostic information also in this clinical context.

232

A Real-World Evidence Study of CDK4/6 Inhibitor Treatment

Patterns and Outcomes in Metastatic Breast Cancer by

Gbrcamutation Status

Michael Untch1, Peter Andreas Fasching2, Kimmie Mclaurin3

1Helios Klinikum Berlin-Buch, Berlin, Deutschland

2Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Deutschland

3AstraZeneca Pharmaceuticals, AstraZeneca Pharmaceuticals, Gaithersburg,

United States

Purpose: Limited data exist on the real-world treatment patterns and ef-

fectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in

the germlineBRCA(gBRCA) mutated breast cancer population.

Methods: Adults with human epidermal growth factor receptor 2 nega-

tive (HER2-), hormone receptor positive (HR+) metastatic breast cancer

(mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were

retrospectively selected from the Flatiron Health Oncology electronic

medical record database. Patients with known gBRCAstatus were clas-

sied as having gBRCA mutated (gBRCAm) or wild type (gBRCAwt)

disease. Time to rst subsequent therapy or death (TFST) and overall sur-

vival (OS) were calculated from start of the earliest line of therapy with

a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and

TFST and OS compared between gBRCAgroups with Cox models strat-

ied by line of therapy and adjusting for demographic and clinical char-

acteristics that modied hazard ratios (HRs) for gBRCAstatus by > 10%.

Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 in-

hibitor, gBRCAstatus was known for 859 (28.9%). Patients with gBRCAm

and gBRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respec-

tively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6

regimens (24.7 and 29.5%) across all lines. e gBRCAm group had a

non-signicant, shorter TFST than gBRCAwt (stratied HR 1.24; 95% CI

0.96–1.59). OS was signicantly shorter in gBRCAm than gBRCAwt pa-

tients (stratied HR 1.50; 95% CI 1.06–2.14).

Conclusions: e results of this real-world study suggest that treat-

ment outcomes with CDK4/6 inhibitors may be poorer in patients with

gBRCAm compared with gBRCAwt disease. ese ndings indicate a

higher unmet need among patients with gBRCAm, potentially requiring

alternative treatment options.

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254

Routine Care of Advanced Breast Cancer: The Prospective,

National Research Platform Opal for Patients with Advanced

Breast Cancer in Germany

Thomas Decker 1; Nadia Harbeck 2; Marc Thill 3; Mark-Oliver Zahn 4;

Arnd Nusch 5; Andreas Lorenz 6; Ulrike Söling 7; Marco Chiabudini 8;

Lisa Kruggel 8; Martina Jänicke 8; Norbert Marschner 9; Elmar Stickeler 10;

Achim Wöckel 11; Anja Welt 12

1Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,

Deutschland

2Brustzentrum, Klinik der Universität München (LMU), München, Deutschland

3Agaplesion Markus Krankenhaus, Frankfurt a.M., Deutschland

4Überörtliche Berufsausübungsgemeinschaft, Goslar, Deutschland

5Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland

6Frauenarztpraxis Dr. Lorenz, Hildburghausen, Deutschland

7Hämato-Onkologisches Zentrum Kassel GmbH, Kassel, Deutschland

8iOMEDICO, Freiburg im Breisgau, Deutschland

9Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br.,

Deutschland

10Universitätsklinikum Aachen AöR für die Medizinische Fakultät, Aachen,

Deutschland

11Universitätsklinikum Würzburg, Würzburg, Deutschland

12Universitätsklinikum Essen (AöR), Essen, Deutschland

Purpose: e Tumor Registry Breast Cancer (TMK) has prospectively

documented treatment and outcome of patients (pts) with breast cancer

(BC) by oncologists in Germany since 2007. OPAL continues this success-

ful work focusing on changes in treatment reality of advanced BC (ABC),

patient-reported outcomes (PROs) and representation of all specialists

(medical and gynecologic oncologists) treating ABC in Germany.

Methods: OPAL like the TMK is a prospective, observational, open, mul-

ticentre clinical registry. In addition to the 4500 pts from the TMK, at least

2000 pts will be recruited in OPAL, stratied into 3 cohorts: 1000 pts with

hormone receptor positive, HER2-negative, 500 pts with HER2-positive

and 500 pts with triple-negative ABC. In total, up to 200 sites (compre-

hensive cancer centres, clinics and oce-based gynecologic and medical

oncologists) will be participating. All pts are recruited at start of their rst

palliative systemic treatment to avoid overestimation of outcome data.

OPAL collects detailed information on all (sequential) treatments, patient

and tumor characteristics, physician-reported factors inuencing treat-

ment decision, biomarker testing and additional treatments. Follow-Up

is until death or up to 5 years. Associated projects are a decentralized bio-

bank and the collection of PROs in clinical routine (every 3 months for

3.5 years).

Results: By August 2019, a total of 5319 pts had been recruited, 677 since

the start of OPAL in December 2017. 2348 pts with ABC recruited by 130

sites are now available for analyses of the combined TMK/OPAL database.

First results from the interim analysis 2019 will be presented.

Conclusions: OPAL will show how the choice of treatment changes over

time, which sequential treatments are applied and what the eectiveness

and PROs are in a “real world” setting. It will reveal the impact of new

treatments in pts in routine care and allow to identify areas for improve-

ment of care.

Disclosure Statement: None of the authors declare conicts of interests regarding

the topic of this abstract.

257

Skeletal-Related Events in Patients with Breast Cancer and

Bone Metastases: Frequency, Predictors and Mortality in a

Real-World Setting

Ingo Diel 1; Lennart Hickstein 2; Josephine Jacob 2; Eugen Dornstauder 3;

Michael Kellner 3; David Hohmann 4

1Mannheim, Praxisklinik am Rosengarten, Mannheim, Deutschland

2Berlin, InGef - Institut für angewandte Gesundheitsforschung Berlin GmbH,

Berlin, Deutschland

3München, Amgen GmbH, München, Deutschland

4München, Privater Beitrag: Früher Amgen GmbH, München, Deutschland

Purpose: Breast cancer is the most common cancer among women

in Germany with more than 70,000 new cases per year. In contrast the

mortality rate is much lower (20%). A large proportion of patients with

advanced disease are aected by bone metastases, or BM, (80%) and

skeletal-related events (SREs) resulting from BM. Moreover, observational

studies of patients with prostate cancer and BM have shown an association

between an increase of SREs and poorer survival. is study aims to

investigate this association in breast cancer patients with BM in a real-

world setting.

Methods: Data were obtained for analysis from the health claims InGef

database and limited to female breast cancer patients with newly diag-

nosed BM between 2012 and 2015. Event rates (ER) for distinct SREs were

calculated per 5 person-years (PY). In addition, using a time dependent

multivariate cox regression, we rst quantied the association between

SREs and all-cause death and second, through an exploratory analysis, we

evaluated the relation between use of bone-targeted agents (BTAs) and

SREs.

Results: e study population comprised of 2,522 female breast cancer

patients with a mean age of 65,8 years (SD +/- 13,0). ER per 5 PY var-

ied in frequency starting from radiation to the bone (ER=1.72), surgery

to the bone (ER=0.53) and pathologic fractures (ER=0.47) to spinal cord

compression (ER=0.07). Signicant associations (p<0,05) for a higher

risk of all-cause death were identied for the SREs pathologic fractures

(HR=2.41, 95% CI: 2.06-2.81) and radiation to the bone (HR=1.55, 95%

CI: 1.39-1.74). Finally, an exploratory analysis revealed that patients treat-

ed with BTAs experienced a 42% reduction in the risk of developing SREs

(HR=0.58, 95% CI: 0.47-0.71).

Conclusions: Our study shows that pathologic fractures and radiation

to the bone are common SREs in advanced breast cancer patients, both

leading to a higher risk of earlier death in this population. Treatment with

BTAs reduce the risk of developing SREs and therefore may lead to longer

survival in these patients.

Conicts of Interest:

is study was sponsored by Amgen GmbH which provided funding to WIG2

GmbH for the execution of the study and medical writing support. InGef –

Institute for Applied Health Research Berlin GmbH acted as subcontractor and

received funding from WIG2 GmbH for the execution of the study and medical

writing support.

Ingo Diel has received consulting fees for participation in advisory boards and has

given several presentations at speakers’ bureaus for Amgen.

Eugen Dornstauder is an Amgen employee and holds Amgen stock.

Robert Bartsch is an Amgen employee and holds Amgen stock.

Michael Kellner is an Amgen employee and holds Amgen stock.

Lennart Hickstein is an employee of InGef – Institute for Applied Health Research

Berlin GmbH and received funding from WIG2 GmbH for the execution of the

study and medical writing support

Josephine Jacob is an employee of InGef – Institute for Applied Health Research

Berlin GmbH and received funding from WIG2 GmbH for the execution of the

study and medical writing support.

David Hohmann was an Amgen employee during conduction of the analysis.

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Male and Female Breast Cancer: a Comparison of a 15-Year

Population-Based Cohort

Simone Schrodi 1; Michael Braun 2; Anne Andrulat 2; Sven Mahner 3;

Nadia Harbeck 3; Marion Kiechle 4; Stefan Paepke 4; Andreas Schnelzer 5;

Christian Schindlbeck 6; Ingo Bauerfeind 7; Claus Belka 8;

Stephanie E. Combs 9; Doris Mayr 10; Wilko Weichert 11; Jutta Engel 12

1Munich Cancer Registry (MCR), Bavarian Cancer Registry – Regional Centre

Munich (LGL) at the Institute of Medical Information Processing, Biometry and

Epidemiology (IBE), , München, Deutschland

2Red Cross Breast Centre, München, Deutschland

3Department of Gynecology and Obstetrics, Breast Centre, University Hospital,

LMU Munich, München, Deutschland

4Department of Obstetrics and Gynecology, University Hospital, Technical

University Munich, München, Deutschland

5Department of Obstetrics and Gynecology, RoMed Kliniken, Breast Centre,

Rosenheim, Deutschland

6Department of Obstetrics and Gynecology, Breast Centre, Klinikum Traunstein,

Traunstein, Deutschland

7Klinikum Landshut, Breast Centre, Landshut, Deutschland

8Department Radiation Oncology, University Hospital, LMU Munich, München,

Deutschland

9Department Radiation Oncology, Technical University Munich, München,

Deutschland

10Department of Pathology, LMU Munich, München, Deutschland

11Department of Pathology, Technical University Munich, München,

Deutschland

12Munich Cancer Registry (MCR), Bavarian Cancer Registry – Regional Centre

Munich (LGL) at the Institute of Medical Information Processing, Biometry

and Epidemiology (IBE), University Hospital, Munich, Germany, München,

Deutschland

Purpose: e aim was to compare prognostic factors, treatment, and out-

come of male and female breast cancer patients.

Methods: A total of 467 men and 58,484 women diagnosed with breast

cancer between 2002 and 2016 in the catchment area of the Munich Can-

cer Registry (MCR) were included in this analysis. A descriptive analy-

sis of prognostic factors and treatment, a comparison of outcome using

the Kaplan-Meier method, cumulative incidence (CI) in consideration of

competing risks and multivariate Cox regression analysis were conducted.

Results: At the time of diagnosis aected men were about 5 years older

than women (mean age 68 vs. 63 years). e proportion of T3/4- tumors

(16% vs.11%), positive lymph nodes (45% vs. 36%), and primary metasta-

ses (9% vs. 7%) was higher in men. Biologically, 99% of male tumors were

endocrine sensitive (vs. 87%) and 6% were HER2/neu positive (vs. 15%).

Men underwent more mastectomies (90% vs. 27%) and less radiotherapy

(44% vs. 71%). Frequencies of axillary surgery, chemotherapy, and endo-

crine therapy were not statistically dierent.

e time to local recurrence (TTL) was also similar in both groups. e

CI in time to metastasis (TTM) was higher in men (12% vs. 8% aer 5

years), however this dierence was not statistically signicant. Respective

multivariate cox-regression analysis also showed no signicant gender

dierences.

Survival improved slightly between 2002-2008 and 2009-2016, but only in

female patients. Survival was lower in men than in women, and this dif-

ference was greater for overall survival (OS) than for relative survival (RS)

(10-year-OS: 56% vs. 70%; 10-year-RS: 78% vs. 81%). Aer adjusting for

prognostic factors, the univariate hazard ratio declined from 1.8 (95%-CI

1.5-2.1) to 1.3 (1.1-1.5).

Conclusions: Probably, delayed diagnosis of breast cancer in male pa-

tients lead to a more advanced tumor stage. Aer adjusting for prognostic

factors, TTM was similar, whereas a statistically signicant dierence in

OS remained. Whether this nding is attributable to dierences in health/

lifestyle/other factors remains to be seen.

269

When Breast Cancer Wants to Spread, Suppress CYR61/CCN1

Johanna Hellinger; Hüchel Silke; Lena Goetz; Gerd Bauerschmitz;

Günter Emons; Carsten Gründker

UMG, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland

Purpose: Matricellular proteins modulate tumor micro environment and

are recognized to contribute to tumor cell invasion and dissemination.

CYR61, member of the CCN family of matricellular proteins, is upreg-

ulated in mesenchymal transformed and invasive breast cancer cells and

correlates with poor prognosis of breast cancer patients. Yet the signaling

whereby cancer cells gain invasive properties with regards to the epitheli-

al-mesenchymal transition (EMT) needs further research.

Methods: Mesenchymal transformed breast cancer cell lines were gen-

erated using prolonged mammosphere cultivation. Microarray analysis,

quantitative PCR and immune/histochemical approches were used to

analyze gene expression alterations upon CYR61 expression regulation

in 4 highly invasive breast cancer cell lines. Transient gene silencing was

conducted using RNA interference. Proliferation was assessed using Ala-

marBlue Assay. To examine the prognostic value of CYR61 and S100A4

expression in 239 patient samples immune-histochemical analysis were

performed.

Results: We investigated the use of CYR61 as a therapeutic target and

prognostic marker for invasive breast cancer and metastasis. Our data in-

dicates that CYR61 regulates metastasis-associated protein S100A4. Sup-

pression of CYR61 reduces the expression of S100A4 through changes in

ERK1/2 activation. Treatment with extracellular CYR61 increased tumor

cell invasion of non-invasive breast cancer cells. Immune-histochemical

analysis of 239 patient tissue samples revealed that higher CYR61 and

S100A4 expression correlates with invasive breast cancer and metastasis.

Conclusions: Our data suggest that CYR61 regulates cancer cell invasion

in highly invasive and aggressive breast cancer cells by altering S100A4 ex-

pression. ese ndings identify mechanism by which CYR61 suppresses

cell invasion and suggest it to be a potential therapeutic target and prog-

nostic marker for invasive breast cancer and metastasis.

Disclosure Statement: e authors declare no disclosures.

270

Palbociclib Plus Fulvestrant as First-Line Therapy for Patients

with Locally Advanced, Inoperable or Metastatic HR+/HER2-

Breast Cancer in Germany: Interim Results of the Inge-B Phase

2 Study

Anja Welt 1; Manfred Welslau 2; Diana Lüftner 3; Mustafa Deryal 4;

Rüdiger Liersch 5; Jörg Sahlmann 6; Leonora Houet 6; Karin Pottho 6;

Norbert Marschner 7; Corinne Vannier 6

1Universitätsklinikum Essen, Innere Klinik, Essen, Deutschland

2MVZ, Klinikum Aschaenburg, Aschaenburg, Deutschland

3Charité, Campus Mitte, Berlin, Deutschland

4Caritasklinik St. Theresia, Frauenheilkunde, Saarbrücken, Deutschland

5Hämatologisch-Onkologische Gemeinschaftspraxis, Münster, Deutschland

6iOMEDICO AG, Freiburg, Deutschland

7Praxis für Interdisziplinäre Onkologie, Freiburg, Deutschland

Purpose: In the PALOMA-3 trial, palbociclib plus fulvestrant demon-

strated a clinically meaningful improvement in overall survival compared

with fulvestrant plus placebo in patients (pts) with hormone receptor-pos-

itive (HR+), HER2-negative (HER2-) metastatic breast cancer who had

relapsed or progressed on prior endocrine therapy (Turner NC et al.,

NEJM 2018). Detailed analyses for rst-line (1L) and later- line (2L+)

therapy are still limited.

Methods: e prospective, multicenter phase 2 INGE-B trial was designed

to generate ecacy and safety data on the combination of palbociclib with

aromatase inhibitors or fulvestrant (1L, 2L+). is pre-planned interim

analysis was conducted to evaluate data on pts receiving palbociclib plus

fulvestrant as 1L or 2L+ therapy. e primary objective was the clinical

benet rate (CBR) in pts with measurable disease according to RECIST

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2018

Index

2018

v1.1. Key secondary endpoints included the overall response rate (ORR),

the CBR for all pts, and safety. Data were analyzed with descriptive

statistics.

Results: At the cut-o date of the interim analysis (Dec 17, 2018), 124

pts have been recruited to receive palbociclib plus fulvestrant (1L: 57 pts;

2L+: 67 pts). Of those, 54 pts treated in 1L were evaluable. Median age

was 69.5 years, 96.3% of pts had an ECOG performance score of 0 or 1.

31.5% (n=17) of pts had non-measurable bone-only disease. e CBR was

58% (n=21) for the 36 pts with measurable disease (RECIST v1.1) and

65% (n=35) for all pts (investigator assessment). Grade 3/4 adverse events

experienced by at least 10% of pts were neutropenia (n=17, 31.5%) and

leukopenia (n=8, 14.9%).

Conclusions: is INGE-B interim analysis showed for the rst time a

remarkable clinical benet for palbociclib plus fulvestrant as rst-line

therapy for pts with HR+/HER2- advanced breast cancer. No new safety

signals emerged.

Reference:

1. Welt A et al., Annals of Oncology (2019) 30 (suppl_3)

Disclosure Statement: AW, Advisory Boards: AstraZeneca, Novartis, Roche, Eisai,

Pzer, Amgen, Lilly; Fees: COCS GmbH, iOMEDICO AG, Interplan AG; Funding

of scientic programs: Novartis. DL, Member of Advisory Board with Amgen,

Novartis, Eli Lilly, Pzer, Celgene and Astra Zeneca; Corporate-sponsored research

by Novartis. MW, Advisory board or board of directors: Amgen, Bristol-Myers

Squibb, Celgene, GILEAD, HEXAL, Janssen, Lilly, medac, NOVARTIS, Roche,

SANOFI; Corporate-sponsored research with AMGEN, Astellas, Astra Zeneca,

Celgene, GILEAD, HEXAL, Janssen, Lilly, NOVARTIS, Roche. NM, Employ-

ment or Leadership Position: iOMEDICO, Stockholder Ownership: iOMEDICO,

Financing of Scientic Research: Pzer

272

Palbociclib Plus Fulvestrant as Second- or Later-Line Therapy

for Patients with Locally Advanced, Inoperable or Metastatic

HR+/HER2- Breast Cancer in Germany: Interim Results of the

Inge-B Phase 2 Study

Diana Lüftner 1; Manfred Welslau 2; Rüdiger Liersch 3; Mustafa Deryal 4;

Cosima Brucker 5; Jaqueline Rauh 6; Anja Welt 7; Matthias Zaiss 8;

Jörg Sahlmann 9; Leonora Houet 9; Corinne Vannier 9; Karin Pottho 9;

Norbert Marschner 8

1Charité, Campus Mitte, Berlin, Deutschland

2MVZ, Klinikum Aschaenburg, Aschaenburg, Deutschland

3Hämatologisch-Onkologische Gemeinschaftspraxis, Münster, Deutschland

4Caritasklinik St. Theresia, Saarbrücken, Deutschland

5Klinikum Nürnberg, Nürnberg, Deutschland

6Gemeinschaftspraxis Innere Medizin, Witten, Deutschland

7Universitätsklinikum Essen, Essen, Deutschland

8Praxis für Interdisziplinäre Onkologie, Freiburg, Deutschland

9iOMEDICO AG, Freiburg, Deutschland

Purpose: In the PALOMA-3 trial, palbociclib plus fulvestrant demon-

strated a clinically meaningful improvement in overall survival compared

with fulvestrant plus placebo in patients (pts) with hormone receptor-pos-

itive (HR+), HER2-negative (HER2-) metastatic breast cancer who had

relapsed or progressed on prior endocrine therapy (Turner NC et al.,

NEJM 2018). Detailed analyses for rst-line (1L) and second- or later- line

(2L+) therapy are still limited.

Methods: e prospective, multicenter phase 2 INGE-B trial was designed

to generate ecacy and safety data on the combination of palbociclib with

aromatase inhibitors or fulvestrant (1L, 2L+). is pre-planned interim

analysis was conducted to evaluate data on pts receiving palbociclib plus

fulvestrant as 1L or 2L+ therapy. e primary endpoint was the clinical

benet rate (CBR) in pts with measurable disease according to RECIST

v1.1. Key secondary endpoints included the overall response rate (ORR),

the CBR for all pts, and safety. Data were analyzed with descriptive

statistics.

Results: At the cut-o date of the interim analysis (Dec 17, 2018), 124

pts have been recruited to receive palbociclib plus fulvestrant (1L: 57 pts;

2L+: 67 pts). 57 of 67 pts treated in 2L+ were evaluable. Median age was

68.0 years, 91.2% (n=52) of pts had an ECOG performance score of 0 or

1. 28.1% (n=16) of pts had non-measurable bone-only disease. e CBR

was 35% (n=14) for the 40 pts with measurable disease (RECIST v1.1) and

51% (n=29) for all pts (investigator assessment). Grade 3/4 adverse events

experienced by at least 10% of pts were neutropenia (n=21, 36.8%) and

leukopenia (n=7, 12.3%).

Conclusions: is INGE-B interim analysis showed a remarkable clinical

benet for palbociclib plus fulvestrant as second- or later-line therapy for

pts with HR+/HER2- advanced breast cancer. No new safety signals were

detected.

Reference:

1. Lüner D et al., ESMO 2019, #1423

Disclosure Statement: DL, Advisory board or board of directors: Amgen, Eli Lilly,

Celgene, Novartis, Pzer, Teva, Tesaro, Loreal, MSD, Astra Zeneca; Corporate-

sponsored research with Amgen, Novartis; MW, Advisory board or board of

directors: Amgen, Bristol-Myers Squibb, Celgene, GILEAD, HEXAL, Janssen,

Lilly, medac, NOVARTIS, Roche, SANOFI; Corporate-sponsored research with

AMGEN, Astellas, Astra Zeneca, Celgene, GILEAD, HEXAL, Janssen, Lilly,

NOVARTIS, Roche, SANOFI; AW, Advisory board or board of directors: Roche,

Novartis, AstraZeneca, Lilly, Eisai, Pzer, Amgen; Corporate-sponsored research:

Novartis (scientic grant);NM, Employment or Leadership Position: iOMEDICO,

Stockholder Ownership: iOMEDICO, Financing of Scientic Research: Pzer

300

Long-Term Adjuvant Therapies for Breast Cancer are

Over-Treatments

Dieter Hölzel 1; Gabriele Schubert-Fritschle 2; Jutta Engel 2

1Tumorregister München Ludwig-Maximilians-Universität, München,

Deutschland

2Tumorregister München, Ludwig-Maximilians-Universität, München,

Deutschland

Purpose: Breast cancer guidelines recommend adjuvant endocrine ther-

apies (EAT) for 10 years because randomized trials with tamoxifen im-

proved survival by 2.8% aer 15 years. However, there is no convincing

reason for a long duration of treatment.

Methods: ese ndings are based on known facts and studies on inci-

dence, growth and diagnosis of primary breast cancer (PT) and its metas-

tases (MET). Many studies have shown the eect of neoadjuvant and ad-

juvant therapies on manifest and occult PTs and their METs. When these

therapies are shortened, prolonged, delayed or interrupted inconsistencies

between eects, duration of treatment and treatment windows arise.

Results: e survival benet of EATs is real, but EATs are not evi-

dence-based. Extensions aer 1, 2 or 5 years have no eect on surviv-

al for 5 years each, although 49%, 42% or 28% of all METs occur at

these intervals. If therapies are delayed by months or years, the ef-

fects are comparable to those of primary treatment without delay,

but all METs expected without therapy appear in the delay phase.

e 2.8% eect is achieved by “chemoprevention”, the neoadjuvant treat-

ment of ipsilateral and contralateral occult second malignancies, which

eradicate 50% and with them about 25% of their expected METs. e

eect size is determined by the higher risk of secondary breast cancers.

But for the duration of the prevention of 5 years, there are no convincing

explanations. Due to the slow growth of the PTs and the large treatment

window, in which newly emerging up to almost detectable PTs are rapidly

eradicated, these EATs can be interrupted without disadvantage and the

therapy can be signicantly de-escalated.

Conclusions: From known facts can be deduced: Intermittent therapies

can reduce long-term therapies by 70-80% with equal eect. Less side ef-

fects with a higher quality of life and better survival rates through higher

compliance would be a therapy innovation for almost one million breast

cancer patients in Germany alone. e challenge for optimal duration is:

how short is short enough.

Disclosure Statement: No conict of interest.

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310

Circulating Non-Coding RNA – Biomarker Potential in

Neoadjuvant Chemotherapy of Triple Negative Breast Cancer?

Marc Hirschfeld 1, 2, 3; Andrea Ritter 1, 2; Kai Berner 1, 2; Gerta Rücker 4;

Markus Jäger 1, 2; Daniela Weiß 1, 2; Markus Medl 1, 2; Claudia Nöthling 1, 2;

Sandra Gassner 1, 2; Jasmin Asberger 1, 2; Thalia Erbes 1, 2

1Department of Obstetrics and Gynecology, Medical Center – University of

Freiburg, Freiburg, Deutschland

2Faculty of Medicine, University of Freiburg, Freiburg, Deutschland

3Institute of Veterinary Medicine, Georg-August-University Goettingen,

Goettingen, Deutschland

4Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical

Center - University of Freiburg, Freiburg, Deutschland

Purpose: Early response to neoadjuvant chemotherapy (NACT) is highly

associated with benecial outcome in breast cancer (BC) patients espe-

cially in triple negative (TNBC) and Her2 enriched molecular subtypes.

Non-coding RNAs (ncRNAs) such as microRNAs (miR) are involved in

carcinogenesis and cell proliferative processes where they can act either

as tumor suppressors or as oncogenes. Liquid biopsy-based ncRNA bio-

markers might represent valuable innovative tools in the prediction of

NACT response of TNBC patients improving patients’ outcome.

Methods: One triple positive (BT-474) and three triple negative (BT-20,

HS-578T, MDA-MB-231) breast cancer cell lines were treated with cyto-

static drugs (carboplatin, epirubicin, gemcitabine and paclitaxel). Intra-

and extracellular evaluation of 12 microRNAs, 1 piRNA and 1 tRNA ex-

pression proles were performed by extracellular vesicular RNA-isolation

and subsequent qRT-PCR. Relative quantication was performed accord-

ing to Busk et al. 2014. Eight TNBC patients as well as ten healthy women

provided serum and urine specimen. ncRNA expression level comparison

was performed applying two-sample t-test. Preliminary, samples of TNBC

patients were compared at two time points.

Results: Distinct ncRNA expression alterations in (TN)BC cell lines in

both the intra- and extracellular compartment were observed aer che-

motherapeutic treatment. Serum and urine-based ncRNA expression

identied as applicable tool to discriminate TNBC vs. controls. Time

point comparison of TNBC urine samples revealed a general ncRNA rise.

Serum data identied diversely, implying a potential correlation with an

NACT-driven clinical complete response.

Conclusions: is study provides new insights into the involvement of a

BC-related ncRNA panel in the response of TNBC to NACT both in vitro

and in vivo. On the one hand, distinct ncRNA expression proles could

help to improve TNBC diagnosis. On the other hand, monitoring of se-

rum or urine ncRNA levels mightt contribute to TNBC therapy response

management with the goal of improving patients` outcome.

328

Monarch 2: Interim Overall Survival of Abemaciclib Plus

Fulvestrant in Patients with HR+, HER2Advanced Breast

Cancer

Eva Maria Grischke 1; George W Sledge 2; Masakazu Toi 3; Patrick Neven 4;

Joo Hyuk Sohn 5; Kenichi Inoue 6; Xavier Pivot 7; Olga Burdaeva 8;

Norikazu Masuda 9; Peter Kaufman 10; Han Koh 11; Pierfranco Conte 12;

Susana Barriga 13; Karla Hurt 13; Martin Frenzel 13; Stephen Johnston 14;

Antonio Llombart-Cussac 15

1Tübingen, Universität Tübingen, Tübingen, Deutschland

2Stanford, Stanford University School of Medicine, Stanford, United States

3Präfektur Kyōto, Graduate School of Medicine, Japan

4Löwen, Universitaire Ziekenhuizen Leuven, Löwen, Belgien

5Seoul, Yonsei Cancer Center, Seoul, Südkorea

6Präfektur Saitama, Saitama Cancer Center, Japan

7Straßburg, Centre Paul Strauss, Straßburg, Frankreich

8Archangelsk, Arkhangelsk Regional Clinical Oncology Dispensary, Archangelsk,

Russland

9Ōsaka, NHO Osaka National Hospital, Ōsaka, Japan

10Burlington, University of Vermont Cancer Center, Burlington, United States

11Bellower, Kaiser Permanente, Bellower, Bellower, United States

12Padua, University of Padova, Padua, Italien

13Indianapolis, Eli Lilly and Company, Indianapolis, United States

14London, The Royal Marsden NHS Foundation Trust, London, United Kingdom

15Valencia, Hospital Arnau Vilanova, Valencia, Spanien

Purpose: In MONARCH 2, abemaciclib+fulvestrant signicantly im-

proved progression-free survival (PFS) vs placebo+fulvestrant (median:

16.4 vs 9.3 months, HR: 0.553) with a tolerable safety prole.

Methods: MONARCH 2 was a global, randomized, double-blind phase3

trial of abemaciclib+fulvestrant (N=446) or placebo+fulvestrant (N=223)

in women with advanced endocrine therapy (ET)-resistant hormone re-

ceptor-positive (HR+), human epidermal growth factor receptor 2-neg-

ative (HER2-) advanced breast cancer (ABC). ET resistance was dened

as progression on (neo)adjuvant ET, or ≤12 months from end of adju-

vant ET, or on rst-line ET for metastatic BC. Patients with measurable

disease (per RECIST v1.1) or nonmeasurable bone-only disease and any

menopausal status were included (pre- or perimenopausal women also

received a gonadotropin-releasing hormone agonist). Prior chemotherapy

was permitted only in (neo)adjuvant setting. 669 patients were random-

ized 2:1, stratied based on nature of disease (visceral, bone-only, or other

metastases) and resistance to prior ET (primary vs secondary). Abemac-

iclib or placebo 150mg was dosed Q12H, and fulvestrant 500mg was ad-

ministered per label. e primary objective was investigator-assessed PFS.

OS is an important secondary endpoint. e family-wise type I error is

controlled at 0.025 (1-sided), with a gate-keeping strategy between PFS

and OS. For OS, an α-spending function will be used to account for in-

terim and nal analyses. OS will be compared using a 1-sided stratied

log rank test.

Results: e preplanned interim OS analysis at approximately 331 events

will be conducted and presented at the meeting.

Conclusions: Following the preplanned interim OS analysis, the associat-

ed conclusions will be presented at the meeting.

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2018

330

Monarcher: A Randomized Phase 2 Study of Abemaciclib Plus

Trastuzumab with or without Fulvestrant Versus Trastuzumab

Plus Standard-of-Care Chemotherapy in Women with HR+,

HER2+ Advanced Breast Cancer

Johannes Ettl 1; Sara Tolaney 2; Andrew Wardley 3; Stefania Zambelli 4;

John F Hilton 5; Francesco Ricci 6; Seock-Ah Im 7; Sung-Bae Kim 8; Stephen

Johnston 9; Arlene Chan 10; Shom Goel 11; Kristen Catron 12; Zhengyu Yang 12;

Corona Gainford 12; Fabrice Andre 13

1München, Technische Universität, München, Deutschland

2Boston, Harvard University, Boston, United States

3Manchester, University of Manchester, Manchester, United Kingdom

4Mailand, IRCCS Ospedale San Raaele, Mailand, Italien

5Ottawa, The Ottawa Hospital and University of Ottawa, Ottawa, Kanada

6Paris, Institute Curie, PSL Research University, Paris, Frankreich

7Seoul, Seoul National University College of Medicine, Seoul, Südkorea

8Seoul, Asan Medical Center, Seoul, Südkorea

9London, Royal Marsden Hospital, London, United Kingdom

10Nedlands, reast Cancer Research Centre - WA and Curtin University, Nedlands,

Australien

11Boston, Dana-Farber Cancer Institute, Boston, United States

12Indianapolis, Eli Lilly and Company, Indianapolis, United States

13Villejuif, Université Paris Sud, Villejuif, Frankreich

Purpose: Abemaciclib showed ecacy and tolerability in patients (pts)

with HR+, HER2- advanced breast cancer (ABC). In preclinical models,

inhibition of CDK4 by abemaciclib enhanced the activity of HER2-direct-

ed agents and re-sensitized resistant tumors to HER2 blockade, suggesting

a crosstalk between HER2 signaling and the cyclin D1/CDK4 signaling

pathways in HER2+ BC.We report the eect of abemaciclib in pts with

HR+, HER2+ ABC.

Methods: monarcHER is a Phase 2 study comparing the ecacy of abe-

maciclib (150mg PO Q12H on Days 1-21 of a 21-day cycle)+trastuzumab

(IV infusion on Day 1 of 21-day cycle) with fulvestrant (F; 500mg IM on

Cycle 1 D1 and D15 and Cycle 2 D8, then Q4W; Arm A) or without F

(Arm B) vs trastuzumab+standard-of-care chemotherapy (per label on

21-day cycle; Arm C) in pts with HR+, HER2+ ABC. Eligible pts were

postmenopausal women with ≥2 HER2-directed therapies for advanced

disease and received prior T-DM1 and taxane in any disease setting,

had ECOG PS ≤1, and LVEF ≥50%. 237 pts were randomized 1:1:1 and

stratied based on the number of prior systemic regimens (excluding sin-

gle-agent ET) for ABC (2 to 3 vs 3+) and nature of the disease (measurable

vs nonmeasurable). Primary objective was to compare the PFS of Arm A

and B to Arm C. Secondary objectives included OS, response evaluation,

safety, ecacy, and pharmacokinetics. e primary analysis was planned

at ~165 PFS events, providing 80% statistical power to detect superiority

of Arm A over Arm C, assuming a HR of .667 at 1-sided α=.1.

Results: e monarcHER study was conducted in 14 countries. e last

patient entered treatment on February 28, 2018. e data from the prima-

ry analysis for ecacy and safety will be available mid-May 2019.

Conclusions: e conclusion for PFS, objective response rate (complete

response [CR]+partial response [PR]), disease control rate (CR+PR+stable

disease [SD]), clinical benet rate (CR+PR+SD ≥6 months) and safety

data will be presented at the meeting.

363

Secretome Analysis Reveals Driver for Bone-Directed Breast

Cancer Invasion

Johanna Hellinger 1; Franziska Schömel 1; Christof Lenz 2, 3;

Gerd Bauerschmitz 1; Günter Emons 1; Carsten Gründker 1

1UMG, Klinik für Gynäkologie und Geburtshilfe, Göttingen, Deutschland

2Max-Planck-Institut für biophysikalische Chemie, Bioanaltytical Mass

Spectrometry Group, Göttingen, Deutschland

3UMG Institute of Clinical Chemistry, Core Facility Proteomics, Göttingen,

Deutschland

Purpose: e tumour metastatic cascade is highly regulated by the mi-

cro environmental changes. Drugs are needed to modify the breast micro

environment, where tumour cells gain the ability to disseminate. Here we

suggest potential drivers of initial dissemination of tumour cells with re-

gards to bone-directed metastasis. While an increased CTGF expression

in human breast cancer correlates with poor patient outcome and drug

resistance (1), a major questions has remained: Will targeting CTGF help

to prevent breast cancer cell dissemination into the surrounding tissue?

And which underlying molecular mechanisms are involved in breast can-

cer directed bone metastasis?

Methods: Here, we apply secretome analysis, proteome analysis and mi-

croarray data to elucidate drivers of epithelial-mesenchymal transition

and cell invasion. Gene ontolgy enrichment analysis led us to the prom-

inent regulated pathways. To examine in vitro invasive properties we as-

sessed 2D invasion in a modied boyden chamber, 3D spheroid invasion,

cell-ECM adhesion and ECM degradation.

Results: CTGF is highly upregulated when MCF-7 non-invasive breast

cancer cells are co-cultured with osteosarcoma cells and gain invasive

properties. Suppression of CTGF reduced invasion and expression of

EMT-related genes. GnRH agonist Triptorelin reduces CTGF expression

in a RhoA -dependent manner.

Conclusions: Our data indicate a mechanism by which extracellular

CTGF drives cell dissemination by regulating cell adhesion, ECM degra-

dation and regulation of EMT inducing factor TGFBI. Moreover it was as-

sessed that CTGF expression is regulated by RhoA activity. e performed

experiments support the value of CTGF as therapeutic target for invasive

breast cancer, and GnRH agonist Triptorelin treatment could be of value

in clinical applications.

Reference:

1. Wells JE, Howlett M, Cole CH, Kees UR. Deregulated expression of connective

tissue growth factor (CTGF/CCN2) is linked to poor outcome in human

cancer. International Journal of Cancer. 2015;137(3):504-11.

Disclosure Statement: e authors declare no disclosures.

378

Micrometastases in Axillary Lymph Nodes and Outcome

of Breast Cancer

Madeleine Hetterich 1; Michael Gerken 2; Olaf Ortmann 1;

Monika Klinkhammer-Schalke 2; Atanas Ignatov 1

1Department of Obstetrics and Gynecology, University Medical Center

Regensburg, Regensburg, Deutschland

2Tumor Center Regensburg, Institute for Quality Assurance and Health Services

Research, University of Regensburg, Regensburg, Deutschland

Purpose: e axillary lymph node status is one of the most important

prognostic factors in patients with primary breast cancer. Micrometas-

tases (pN1mi) are dened as nodal metastases with deposits from >0.2 ≤

2mm. eir impact on overall survival (OS) and recurrence-free survival

(RFS) of patients with breast cancer remains unclear. ere are no rec-

ommendations concerning the performance of adjuvant chemotherapy.

us, the aim of this study was to analyze the eect of micrometastases

on the clinical outcome of patients with breast cancer according to their

adjuvant chemotherapy status.

Methods: We performed a retrospective registry-based study. 26353 pa-

tients were investigated and 14070 were excluded and 12283 were eligible

for analysis: 11743 were identied as pN0 and 540 as pN1mi.

Results: Micrometastases in regional lymph nodes were associated with a

reduced 10-year rate of OS and RFS among women with early-stage breast

cancer, who did not receive systemic adjuvant chemotherapy. e eect

however, was not conrmed in the multivariate analysis aer adjustment

for age, tumor size, grading (etc.). Furthermore, in the group of patients

with micrometastases systemic treatment improved neither the OS (haz-

ard ratio (HR) 1.51, 95% condence interval (CI) 0.80-2.85) (p=0.208)

nor the RFS (HR 1.12, 95%CI 0.63-1.97) (p=0.705) as demonstrated by

multivariate cox-regression analysis.

Conclusions: Chemotherapy did not improve signicantly the outcome

of breast cancer patients with nodal micrometastases. In this regard, nodal

micrometastases should not be considered in our treatment decision.

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Reference:

1. De Bowe et al.: Micrometastases or Isolated Tumor Cells and the Outcome of

Breast Cancer. NEJM. August 13, 2009.

412

Evidence-Based Decision Support System for Breast Cancer

Michael Dück 1; Eberhard Beck 1

1Technische Hochschule Brandenburg, Fachbereich Informatik und Medien,

Brandenburg an der Havel, Deutschland

Purpose: In order to increase the patients’ ability to make their own in-

formed decisions about their breast cancer therapy and to support patient

empowerment in general, it is necessary to provide decision-relevant in-

formation in an understandable mode. is aim will be targeted by gen-

erating computer-based systems which provide the relevant information

resulting in guideline-based decisions.

Methods: By using the evidence-based guidelines for the treatment of

breast cancer1,2 a web-based decision support platform for patients and

health care professionals is being created. e design and content will be

kept up-to-date by involving the target groups in the development.

Results: Two prototypes for an evidence-based decision support platform

were created to test if it was possible to translate the medical guidelines

to a digital rule-based system, which is able to create relevant suggestions

based on the information given by a patient. ose prototypes were eval-

uated by a patient and a health care professional and will be continuously

improved and tested.

Conclusions: e rst evaluations proofed that there is a need for patient

information systems, especially for diseases with a high risk for complica-

tions and a wide eld of treatment options. In order to improve the quality

of shared decision making and thus increase the patients’ compliance with

selected treatment choices, these systems could support the patients by

increasing this decease-related knowledge. e continuous development

and evaluation of evidence-based decision support systems for breast

cancer patients and for other malignant or chronic diseases is one of our

major goals.

References:

1. Interdisziplinäre S3-Leitlinie für die Früherkennung, Diagnostik, erapie und

Nachsorge des Mammakarzinoms, Albert, U, et al.

2. Diagnostik und erapie früher und fortgeschrittener Mammakarzinome,

Janni, W, et al.

Disclosure Statement: e author declares that he has no relevant or material

nancial interests that relate to the research described in this paper

461

Panel-Guided Personalized Medicine in Metastatic Breast and

Gynecological Cancer, First Experiences at te CCC Munich LMU

Elena Sultova 1; Benedikt Westphalen 2; Andreas Jung 3; Thomas Kirchner 3;

Doris Mayr 3; Volker Heinemann 2; Klaus Metzeler 2; Philipp Greif 2;

Fabian Trillsch 4; Sven Mahner 4; Nadia Harbeck 1; Rachel Würstlein 1

1LMU Munich, University Hospital, Department of Obstetrics and Gynecology,

Breast Center and CCC Munich LMU, München, Deutschland

2Klinikum der Universität München , Medizinische Klinik und Poliklinik III und

CCC Munich LMU, München, Deutschland

3Ludwig-Maximilians-Universität München, Pathologisches Institut der LMU

und CCC München LMU, München, Deutschland

4LMU Munich, University Hospital, Department of Obstetrics and Gynecology,

CCC Munich LMU, München, Deutschland

Purpose: Some tumorigenic alterations associated with cancer cell devel-

opment and progression can be therapeutically addressed by molecularly

targeted agents. Comprehensive genomic proling identifying such ac-

tionable alterations aims to oer personalized treatment to cancer patients.

Here, we report rst experiences of the Comprehensive Cancer Center

Munich Molecular Tumor Board (MTB) in breast and gynecologic malig-

nancies. Our aim was to measure the impact of recommendations made

by a multidisciplinary tumor board on the overall survival of patients with

gynecologic cancers, that progressed under standard treatment.

Methods: 99 patients diagnosed with metastatic breast or gynecologic

malignancies underwent molecular diagnostic test (panel). From May

2017 through March 2019, our MTB reviewed the clinical cases carefully

considering tumor prole and discovered genetic aberrations and provid-

ed further diagnostic and therapy recommendations. All patients were

part of a prospective registry (Der informative Patient).

Results: 95 patients with metastatic gynecologic tumors were discussed

in the MTB (68% breast cancers, 20% ovarian cancer, 5% cervical cancer,

3% endometrial cancer and 4% others). e genes with the highest muta-

tion rate were PI3KCA, KRAS, FGFR1 and CCND1. Overall, 34 patients

(36%) received an alteration-specic targeted therapy recommendation.

Recommended therapies included various drugs such as protein-kinase

inhibitors (45%), combination therapies (24%) and clinical trials (20%).

erapeutic recommendations were implemented in 9 cases; 4 patients

experienced a clinical benet with a partial response or stabilization last-

ing over 4 months, including 3 of them receiving o-label treatment.

Conclusions: In the setting of a multidisciplinary molecular tumor board,

a small but clinically meaningful group of breast and gynecologic can-

cer patients derives benet from comprehensive genomic proling. Main

problems of precision cancer medicine include patients’ referral at late

stage disease and limited access to targeted agents.

470

Recommendation of Trastuzumab Therapy for Patients with

Non-Metastatic, HER2/NEU-Positive Breast Cancer: Results

from 3,052 Patients Treated in Certied German Breast Cancer

Centres

Nora Tabea Sibert 1; Christoph Kowalski 1; Clara Breidenbach 1;

Julia Ferencz 2; Sebastian Dieng 2; Elisabeth C. Inwald 3;

Simone Wesselmann 1; Olaf Ortmann 3 and the German Breast Cancer

Centres Participating in the Oncobox Research Project 4

1Deutsche Krebsgesellschaft e.V., Zertizierung, Berlin, Deutschland

2OnkoZert GmbH, Neu-Ulm, Deutschland

3University Medical Center Regensburg, Department of Gynecology and

Obstetrics, Regensburg, Deutschland

Purpose: Since 2006 it is possible to treat non-metastatic, Her2/neu-pos-

itive breast cancer (BC) patients with Trastuzumab in Germany which is

now a highly accepted therapy strategy. Even if the treatment of Her2/

neu-positive BC patients with Trastuzumab is part of the quality indicator

9 of the evidence-based German Guideline for Breast Cancer (S3), recent

studies highlight that there are some Her2/neu-positive BC patients for

whom physicians do not recommend a Trastuzumab therapy (TT). We

investigate for which patients a TT is recommended in Breast Cancer

Centers (BCC) certied by the German Cancer Society and the German

Society for Senology.

Methods: We included Her2/neu-positive, non-metastatic BC patients

(≥ pT1c) treated in German BCCs by surgery between 2006 and 2019. For

3,052 patients, data collected for the certication progress including more

than 150 attributes specifying clinical and treatment characteristics for

each patient were available. A multi-level analysis including these 3,052

patients nested in 17 BCCs was performed.

Results: Recommendation of TT does not dier much between BCCs

(ICC null model: 0.14). Our analysis show that physicians in BCCs more

oen recommend TT to patients who are younger than 69 years and who

had another oncological disease before. Patients with a recommendation

for any additional therapy (chemo-/endocrine therapy, radiation) to sur-

gery receive more likely a recommendation for TT as well (all p < 0.05), if

controlled for T- and N-stage, sex and estrogen- and progesterone-recep-

tor status. Furthermore, there is a signicant increase in recommendation

of TT over the years (frequency of recommendation of TT for patients

treated between 2006 and 2011: 43.4% vs. patients treated between 2012

and 2019: 78.7%).

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Conclusions: In certied German BCCs, the knowledge and acceptance

of guideline-adherent TT is increasing (positive cohort eect). Recom-

mendation of TT for Her2/neu-positive BC patients in BCCs are signi-

cantly associated to age and the recommendations for other additional

therapies apart from surgery.

487

Age-Related Dierences in Overall and Metastases-Free

Survival after Guideline Concordant Chemotherapy in

Patients with Hormone Receptor Positive and Nodal Positive,

Early Breast Cancer

Clara Taubenhansl 1; Olaf Ortmann 2; Michael Gerken 1;

Elisabeth C. Inwald 2; Monika Klinkhammer-Schalke 1

1Tumor Center, Institute for Quality Management and Health Services Research,

University of Regensburg, Regensburg, Deutschland

2Department of Obstetrics and Gynecology, University Medical Center

Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland

Purpose: e German guideline for breast cancer recommends using che-

motherapy (CHT) in patients with hormone receptor positive and nodal

positive, invasive breast cancer. e aim of this study was to analyse the

eects of CHT in this patient group on overall survival (OS) and distant

metastases-free survival (DMFS), especially considering the 70-year

threshold.

Methods: 1772 patients from the clinical cancer registry Regensburg (Ger-

many) with hormone receptor positive and nodal positive, invasive breast

cancer diagnosed between 2003 and 2013 were analysed in a retrospective

cohort study. OS and DMFS were evaluated by means of Kaplan-Meier

and multivariable Cox-regression method. Results were further examined

according to age at diagnosis.

Results: e comparison of 1544 patients with CHT to 228 patients

without CHT showed a signicant benet for CHT regarding 5-years OS

(91.3% vs. 76.8%) and 5-years DMFS (86.7% vs. 74.4%, both p<0.001).

Likewise, better OS and DMFS were seen in patients ages <70 years using

CHT compared to patients without CHT of the same age. Patients ages

>=70 years with CHT had a minimal benet regarding 5-years OS com-

pared to patients without CHT, but no advantage considering DMFS. All

results were conrmed in multivariable analyses except for patients being

>=70 years of age.

Conclusions: Patients with hormone receptor positive and nodal posi-

tive, invasive breast cancer benet from chemotherapy with regard to a

signicantly better overall and distant metastases-free survival, although

chemotherapy use in patients ages >=70 years results in a smaller benet

considering OS and no benet considering DMFS.

Disclosure Statement: e authors declare no conict of interest.

504

Abus as an Alternative to Hand Held Ultrasound for Response

Control in Neoadjuvant Breast Cancer Treatment

Maria Eleni Hatzipanagiotou; Madeleine Hetterich; Blanca Roca Ripoll;

Tanja Eggensberger; Olaf Ortmann; Stephan Seitz

University medical centre Regensburg, Department of Gynecology and

Obstetrics , Regensburg, Deutschland

Purpose: e “Invenia Automated Breast Ultrasound Screening” (ABUS)

for automatic ultrasound examination is indicated as an adjunct to mam-

mography for breast cancer screening in asymptomatic women (approved

by the FDA), for whom screening mammography ndings are normal or

benign but have a high density of breast tissue. ABUS provides ecient

exam reading and analysis within 3 to 6 minutes on the work station (1).

e aim of this study is to evaluate the use of ABUS in patients who are

under neoadjuvant chemotherapy treatment for response control.

Methods: We conducted regular sonographic response check and ABUS

examination in 20 women who were under neoadjuvant chemotherapy

treatment. e hand-held sonography was performed with GE Voluson S8.

e tumor was measured in 3 dimensions. e last sonographic check

took place within the last 4 weeks before the end of chemotherapy. We

compared the hand held sonographic measurement and the ABUS mea-

surement with the size of the pathologic tumor.

Results: We found that there was no signicant dierence between tumor

measurements with hand held ultrasound or ABUS ultrasound in neoad-

juvant response control.

e average dierence from hand held sonographic ultrasound size to nal

pathological tumor size was 9,2 mm. e average dierence from ABUS

ultrasound size to nal pathological tumor size was 8,6 mm (p=0,3). e

median dierence between ABUS and hand held ultrasound tumor size

was 4,8mm.

Conclusions: ABUS seems to be a suitable method to conduct response

control in neoadjuvant breast cancer treatment. ABUS oers remarkable

time saving for physicians compared to handheld ultrasound and thus

should be considered for clinical practice.

Reference:

1. https://www.ge-ultraschall.com/invenia-abus/

Disclosure Statement: n/a.

531

WNT Signaling-Mediated Inhibition of Aromatase

Expression – A Possible Endocrine Model for Triple Negative

Breast Cancers

Alexander Kaiser 1, 2; Martin Schmidt 2; Otmar Huber 2

1Universitätsklinikum Jena - Klinik für Innere Medizin II - Abteilung Hämatologie

und Internistische Onkologie, Jena, Deutschland

2Universitätsklinikum Jena - Institut für Biochemie II, Jena

Purpose: Local biosynthesis by aromatase in breast adipose broblasts

(BAFs) is the most important source for estrogens in estrogen-receptor

positive breast cancers (BC). Triple-negative BC depend on other growth-

promoting signals, e.g. Wnt-signaling. In this study, we investigated the

hypothesis that WNT3a expression in triple-negative BC suppresses

aromatase expression in BAFs.

Methods: Eects of WNT3a and BC cell-conditioned medium (CM) on

BAFs were investigated by cell-proliferation tests, tritium water release and

qRT-PCR assays for aromatase activity and gene expression, respectively.

Protein expression was analyzed by western blotting. A combination of

reporter gene assays, site-directed mutagenesis, protein overexpression

and chromatin immunoprecipitation (ChIP) was used for analysis of tran-

scription factor-binding to dierent binding-sites.

Results: WNT3a and CM of triple-negative breast cancer cells (e.g.

MDA-MB231) increased cell growth and suppressed aromatase activity

and promoter I.3/II-driven gene-expression up to 90%. ree putative

Wnt-responsive elements (WREs) in the aromatase promoter were found.

Promoter activity was inhibited by overexpression of full-length T-cell fac-

tor (TCF)-4 in 3T3-L1 preadipocytes in reporter gene assays. Full-length

lymphoid enhancer-binding factor (LEF)-1 increased activity. However,

WNT3a-stimulation resulted in a loss of TCF-4-binding to WRE1 and

induced a switch of nuclear LEF-1 isoforms to a truncated variant. Over-

expression of truncated LEF-1 inhibited promoter I.3/II-activity. ChIP

revealed a WNT3a-induced replacement of TCF-4 by a LEF-1-variant on

WRE1 of the aromatase promoter I.3/II in BAFs. Switching of LEF-1 iso-

forms may involve canonical Wnt-signaling.

Conclusions: e mechanism described here may contribute to the loss

of estrogen responsibility in the etiology of triple-negative breast cancers.

Strong Wnt-ligand expression by tumors could suppress aromatase ex-

pression in surrounding BAFs.

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540

Impact of Cytotoxic Treatment on PDL1 Expression in Human

Breast Cancer Cell Lines

Peter Ugocsai; Eva-Maria Rom-Jurek; Olaf Ortmann; Stephan Seitz;

Gero Brockho; Anja-Kathrin Wege

Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

Purpose: e oncologic spectrum for the clinical application of check-

point inhibitors (CI) expands rapidly. Clinical trials with CI in breast

cancer (BC) report an overall response rate of up to 19% with durable

clinical responses and tolerable safety proles. Improved understanding

of the immunogenicity of BC under simultaneously applied therapies, e.g.,

cytotoxic treatments, would help to develop more individual therapeutic

strategies to further increase response rates.

Methods: We investigated the expression of PD-L1 on dierent types (tri-

ple negative, luminal-type and HER2-positive) of human BC cell lines and

evaluated the eect of standard chemotherapeutical agents (epirubicin

and paclitaxel) on PD-L1 expression in selected cell lines.

Results: We found greatly varying levels of PD-L1 expression within the

investigated BC cell lines. High PD-L1 expression was found in all three

TNBC- and two of three HER2-overexpressing cell lines. Luminal like tu-

mors seem to express low PD-L1 levels, without great variations. Epiru-

bicin treatment caused a decrease and paclitaxel treatment an increase in

PD-L1 expression in the TNBC MDA-MB-231 cells. In contrast, PD-L1

expression changed to a minor extent in the HER2-overexpressing SK-

BR-3 cell line when exposed to cytotoxic treatments.

Conclusions: e degree of PD-L1 expression among breast cancer cell

lines varies considerably. Our analyses revealed dierent cell type specic

responses to cytotoxic treatments. Furthermore, diverse chemotherapeu-

tic agents engender dissimilar PD-L1 expression changes within the same

cell line, which likely contribute to the varying clinical responses to CI.

Further studies are needed to identify the major mechanisms determining

the immunogenic alterations of BC under chemotherapy.

Disclosure Statement: no conict of interest

547

Prevalence of Critical Values of the Functional and Mental

Status ofBreast CancerPatients Before the Onset of Cancer

Therapy

Niklas Grusdat 1; Alexander Stäuber 1; Henry Schulz 1; Ralf Haase 1;

Marion Tolkmitt 2; Jens Schnabel 2; Birgit Schubotz 3; Dirk-Henrik

Zermann 4; Mark Heydenreich 4

1Chemnitz University of Technology, Professorship of Sports Medicine / Sports

Biology, Chemnitz, Deutschland

2DRK Krankenhaus Chemnitz-Rabenstein, Brustkrebszentrum, Chemnitz,

Deutschland

3Klinisches Krebsregister Chemnitz, Deutschland

4Vogtland-Klinik Bad Elster

Purpose: A reduced functional and mental status even before the cancer

therapy may indicate a worse prognosis for mortality or lower resilience

throughout the dierent stages of cancer treatment. e objective of this

study was to determine the frequency of breast cancer patients demon-

strating parameters of functional and mental status below predicted

threshold values [1-4].

Methods: Within the ‘Return’ study [5] 68 patients with rst diagno-

sis of breast cancer (58±11 yr) in UICC stage 0-IV (0=4.4%, IA=60.3%,

IIA=22.0%, IIB=8.8, IIIA=1.5%, IIIC=1.5%, IV=1.5%) were examined

prior to cancer therapy. Standardised assessment of functional status in-

cluded a handgrip strength test (HGS), 6-minute-walk-test (6MWT) and

BIA for detection of bioimpedance phase angle (pA). e mental status

was investigated using the HADS-A and HADS-D.

Results: 21% of patients presented HGS below individual critical cut-

o value (27.8±5.6 kg). 16% showed a critical pA (5.3±0.9°). In 63% of

patients there was a shorter individual predicted distance in the 6MWT

(470±95m). Clinically relevant (HADS-A and D Score >10) anxiety and

depression scores were diagnosed in 53% and 39% of patients respectively.

18% of breast cancer patients presented with a severe form of anxiety. 16%

were identied with severe symptoms of depression.

Conclusions: e data provides evidence for the occurrence of critical

prognostic values of functional and mental status in breast cancer patients

before cancer therapy. Potential risk factors suggest the adaptation and in-

dividualisation of medical treatment. In order to optimise the treatment,

routine assessments are necessary to establish multidisciplinary interven-

tions. Systematically examining the individual case strengthens the over-

all treatment modalities and can ultimately have a positive impact on the

treatment outcomes.

References:

1. Enright & Sherrill: Am J Respir Crit Care Med 1998

2. Steiber: PLoS One 2016

3. Norman et al: Am J Clin Nutr 2010

4. Stern: Occup Med (Lond) 2014

5. DRKS-ID: DRKS00014263

Disclosure Statement: e authors have nothing to disclose.

552

Application of CDK4/6 Inhibitors in Premenopausal Women

with Hormone Receptor-Positive, HER2-Negative Metastatic

Breast Cancer: a Real-World Experience

Christian M. Kurbacher 1; Lotta Ada Fischer 2; Georg Heinrich 3;

Susanne Herz 1; Alexander Schott 1; A. Tabea Kurbacher 1;

Jutta Anna Kurbacher 4; Christian Rudlowski 5; Mathias R. Warm 2

1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:

Gynäkologische Onkologie), Bonn

2Brustzentrum , Städtisches Klinikum Holweide, Köln

3Praxis für Gynäkologische Onkologie, Fürstenwalde

4Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine

Gynäkologie und Geburtshilfe), Bonn

5Frauenklinik, Evangelisches Krankenhaus Bergisch-Gladbach, Bergisch-

Gladbach

Purpose: Recently, a CDK4/6 inhibitor (CDK4/6i) combined with hor-

monal treatment (HTx) is regarded the most eective rst-line therapy

in premenopausal patients (pts) with hormone receptor-positive (HR+),

HER2-negative (HER-) metastatic breast cancer (MBC). is real-world

compilation of data on HTx combined with a CDK4/6i sought to more ac-

curately estimate the importance of this treatment in the clinical routine..

Methods: A total of 33 premenopausal pts were included. Pts were treated

with a CDK4/6i and HTx consisting of ovarian suppression and an aro-

matase inhibitor (AI) in 23 and fulvestrant in another 10 pts; 23 pts re-

ceived palbociclib and 10 pts were given ribociclib for CDK4/6 inhibition.

11 pts had bone only metastases, 7 pts had visceral metastases and 15 pts

suered from mixed metastatic MBC. 15 pts had received prior systemic

therapy for MBC, comprising Ctx in 5, HTx in 7, and both in 3 pts..

Results: 16 pts (48.5%) are still on treatment with a CDK4/6i+HTx. In

the remainder, therapy was terminated due to disease progression. ere

were no additional signals observed indicating signicant bone marrow,

cardiac, liver, or any other serious toxicity. Median treatment duration is

recently 69.4 weeks. Only 3 pts (13.0%) out of this series have died so far

aer 57.1, 109.7, and 140.6 weeks aer starting CDK4/6i so that the me-

dian overall survival is not yet reached. e 2-year survival proportion is

94.4%, the 3-year survival is 56.0%..

Conclusions: ese data show that CDK4/6i+HTx administered to pre-

menopausal pts with HR+, HER2- MBC is safe and eective in the clinical

routine in both the rst and later line setting and conrm results of the

pivotal randomized clinical trials.

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Care Appropriate to the Needs of Breast Cancer Patients

with Disability – Results of the CANDY-study

Hannah Gröber 1; Anke Groß-Kunkel 2; Holger Pfa 3;

Euphrosyne Gouzoulis-Mayfrank 1; Ute-Susann Albert 4, 5;

Jürgen Zielasek 1; Sophie E. Groß 1

1LVR-Institut für Versorgungsforschung, LVR-Klinik Köln, Köln, Deutschland

2Humanwissenschaftliche Fakultät, Lehrstuhl Pädagogik und Didaktik bei

Menschen mit geistiger Behinderung, Universität zu Köln, Köln, Deutschland

3Institut für Medizinsoziologie, Versorgungsforschung und

Rehabilitationswissenschaft, Humanwissenschaftliche Fakultät und

Medizinische Fakultät, Universität zu Köln, Köln, Deutschland

4Leiterin des Bereichs Senologie und konservative Gynäkoonkologie,

Frauenklinik. Klinikum Kassel , Kassel, Deutschland

5AWMF-Institut für Medizinisches Wissensmanagement, Philipps Universität,

Marburg, Deutschland

Purpose: As life expectancy is increasing in both the general population

and in people with disabilities, the WHO expects a signicant increase in

cancer diseases among people with and without disabilities over the next

decades. Nevertheless, the needs of people with severe, life-threatening

diseases such as cancer and preexisting disabilities are rarely the focus

of health services research. In order to contribute to a need-based health

care for breast cancer patients with disabilities, the CANDY-study aims to

identify barriers and resources, communication diculties and informa-

tion needs of breast cancer patients with disabilities.

Methods: Within the framework of a DFG-funded study (German Re-

search Foundation) (CAre Appropriate to the Needs of breast cancer pa-

tients with DisabilitY) we will conduct 30 interviews with breast cancer

patients with a severely disabled person’s identity card since July 2019.

e patients are recruited in the context of a patient survey for the qual-

ity assurance of breast centers in North Rhine-Westphalia, conducted by

the University of Cologne. e recruitment of breast cancer patients with

various disabilities (physical or sensory impairments, mental illness and

intellectual disability) is performed by means of purposeful sampling. e

interviews are analyzed by content analysis using an inductive and deduc-

tive approach.

Results: So far, there have been 31 positive responses from potential par-

ticipants and the rst interviews have been conducted. e qualitative

analyses of all interviews will be completed by the time of the 34th German

Cancer congress 2020.

Conclusions: Our research aims to clarify the dierent perspectives re-

garding breast cancer care of patients with dierent types of disability.

e CANDY-study will contribute to a more patient-centered provision

of health care for people with disabilities.

Disclosure Statement: none

583

Lung Cancer attributed Mortality among 316,336 Early

Stage Breast Cancer Patients Treated by Radiotherapy or

Chemotherapy, 2000-2015: Evidence from US Cancer Registry

Semaw Abera 1; Rafael Mikolajczyk 2; Eva Johanna Kantelhardt 3;

Christian Ostheimer 4; Dirk Vordermark 4; Daniel Medenwald 1

1Department of Radiation Oncology, Faculty of Medicine and Institute of

Medical Epidemiology, Biostatistics and Informatics (IMEBI), Martin-Luther-

Universität Halle-Wittenberg , Halle (Saale), Deutschland

2 Institute of Medical Epidemiology, Biostatistics and Informatics (IMEBI), Martin-

Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

3Institute of Medical Epidemiology, Biostatistics and Informatics (IMEBI) and

Department of Gynaecology, Faculty of Medicine, Martin-Luther-Universität

Halle-Wittenberg, Halle (Saale), Deutschland

4Department of Radiation Oncology, Faculty of Medicine , Martin-Luther-

Universität Halle-Wittenberg, Halle (Saale), Deutschland

Purpose: To compare lung cancer attributed mortality among early breast

cancer patients, treated by radio-and/or chemotherapy, relative to the US

female general population. Prognostic factors of lung cancer attributed

mortality were also examined.

Methods: Breast cancer data, covering 2000 to 2015 calendar period,

were extracted from the Surveillance, Epidemiology and End Results-18

(SEER-18) cancer registry database. A comparison of lung cancer attribut-

ed mortality between the breast cancer patients and the general popu-

lation was computed using standardized mortality ratios. Prognostic of

factors of lung cancer mortality and the competing causes were identied

using exible parametric modelling.

Results: Compared with the general population, breast cancer patients

who were treated by radio-and/or chemotherapy, only radiotherapy,

radiochemotherapy and only chemotherapy had 37% (95% CI: 39 - 34%),

34% (95% CI: 37 - 31%), 46% (95% CI: 51 - 40%) and 38% (95% CI: 45 -

31%) lower overall mortality from lung cancer, respectively. Lung cancer

mortality was higher for older patients (compared to those <50 years,

HR50-59=3.29 [95%CI:2.65 – 4.10], HR60-69=7.2 [95%CI: 5.80 – 8.86],

HR70-79=10.46 [95%CI: 8.46 – 12.93], and HR80+=10.39 [95%CI: 8.13 –

13.28]) and for those with negative receptors for estrogen and progestron

hormones (HR=1.37; 95% CI: 1.21 – 1.55). Relative to the married,

patients with widowed, divorced, single or other relationships had 69%,

47% and 25% higher hazard of mortality from lung cancer, respectively.

In contrast, lung cancer mortality was lower for American Indian/Alaska

Native and Aisan/Pacic Islander ethnicities (HR=0.49; 95% CI: 0.39 –

0.62) and for those diagnosed at a recent period (HR2011-2015 vs 2000-2005= 0.79;

95% CI: 0.65 – 0.76).

Conclusions: We found no evidence of higher lung cancer attributed

mortality among the breast cancer patients relative to their background

population. e identied factors could be clinically relevant indicators of

lung cancer attributed mortality aer breast cancer diagnosis.

Disclosure Statement: None

585

Breast Cancer Risk in Familial CHEK2 Germline Mutation

Carriers is Modied by the Polygenic Risk Score: A Multicenter

Study by the German Consortium for Hereditary Breast and

Ovarian Cancer

Julika Borde 1; Corinna Ernst 1; Konstantin Weber-Lassalle 1;

Dieter Niederacher 2; Jan Hauke 1; Judit Horvath 3; Nana Weber-Lassalle 1;

Alfons Meindl 4; Auber Bernd 5; Esther Pohl-Rescigno 1; Norbert Arnold 6;

Andrew Lee 7; Christoph Engel 8; Barbara Wappenschmidt 1;

Marjanka Schmidt 9; Antonis Antoniou 7; Rita Katharina Schmutzler 1;

Karoline Kuchenbaecker 10, 11; Eric Hahnen 1

1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology

(CIO), University of Cologne, Faculty of Medicine and University Hospital

Cologne, Cologne, Germany

2Department of Gynaecology and Obstetrics, University Hospital Duesseldorf,

Heinrich-Heine University Duesseldorf, Duesseldorf, Germany

3Institute for Human Genetics, University Hospital Muenster, Muenster,

Germany

4Department of Gynecology and Obstetrics, LMU Munich, University Hospital

Munich, Munich, Germany

5Department of Human Genetics, Hannover Medical School, Hannover,

Germany

6Institute of Clinical Molecular Biology, Department of Gynaecology and

Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-

Albrechts University Kiel, Kiel, Germany

7Centre for Cancer Genetic Epidemiology, Department of Public Health and

Primary Care, University of Cambridge, Cambridge, UK

8Institute for Medical Informatics, Statistics and Epidemiology, University of

Leipzig, Leipzig, Germany

9Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The

Netherlands

10Division of Psychiatry, University College London, Maple House, London, UK

11UCL Genetics Institute, University College London, London, UK

Purpose: Pathogenic CHEK2 germline variants associate with a 20-30%

lifetime risk for female breast cancer (BC). It is suggested that additional

genetic factors, such as BC-associated SNPs identied by GWAS, modify

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individual BC risks. For BRCA1/2 mutation carriers, the combined eects

of BC-associated SNPs (polygenic risk score, PRS) have been shown to be

informative for individual risk stratication. e question arises whether

PRS based risk stratication is applicable for CHEK2 germline mutation

carriers with familial BC.

Methods: Here, we analyzed 904 female CHEK2 germline mutation carri-

ers (585 c.1100delC and 208 carriers of other protein-truncating variants,

111 individuals with pathogenic missense variants). A total of 667 muta-

tion carriers were aected by BC (546 unilateral BC, 121 bilateral BC),

with a mean age at rst/secondary diagnosis of 45.9 (23-89)/49.1 (30-79)

years, respectively. 237 mutation carriers were not aected by BC (mean

age at last follow-up: 43.4 (18-92) years). A cohort-approach including

retrospective and prospective events was applied. Multicenter recruitment

was through genetic counseling centers in Germany including index pa-

tients and relatives over a period of 21 years. Genotyping of 77-and 88

established BC-associated SNPs, respectively, was performed using the

Fluidigm® Access Array with subsequent next generation sequencing. A

weighted cohort approach with age at rst BC diagnosis as outcome was

employed to evaluate the association of standardized PRS with BC risk in

CHEK2 mutation carriers.

Results: PRS values computed on the basis of both PRS sets were statisti-

cally signicant associated with BC risk for CHEK2 carriers. e age-spe-

cic hazard ratio estimates were used to compute absolute cumulative BC

risks for mutation carriers by PRS percentiles. CHEK2 carriers at the 10th

percentile of the PRS had a BC risk of approximately 6% compared to

~18% in the 90th percentile by age 60 years.

Conclusions: Combined genotyping of BC-associated SNPs may improve

personalized risk prediction for CHEK2 mutation carriers.

588

Chemotherapy (CT)-Induced Anaemia in Patients (PTS)

Treated with Dose-Dense Regimen: Results of the

Prospectively Randomised Anaemia Substudy from the

Neoadjuvant Geparocto Study

Hans Tesch 1; Sibylle Loibl 2; Karin Kast 3; Christian Jackisch 4; Volker Möbus 5;

Stefanie Buchen 6; Michael Untch 7; Claus Hanusch 8; Sabine Seiler 2;

Michael Weigel 9; Peter A. Fasching 10; Kerstin Rhiem 11; Jens Huober 12;

Jens-Uwe Blohmer 13; Christine Solbach 14; Carsten Denkert 15;

Valentina Nekljudova 2; Theresa Link 3; Andreas Schneeweiss 16

1Centrum für Hämatologie und Onkologie Bethanien, Frankfurt, Germany,

Frankfurt am Main, Deutschland

2GBG, Neu-Isenburg, Germany

3Universitätsklinikum Dresden, Dresden, Germany, Deutschland

4Sana Klinikum Oenbach, Oenbach, Germany

5Klinikum Frankfurt-Höchst, Frankfurt, Germany

6Asklepios Paulinen Klinik Wiesbaden, Wiesbaden, Germany

7Helios Klinikum Berlin-Buch, Berlin, Germany

8Rotkreuzklinikum, München, München, Germany

9Leopoldina-Krankenhaus, Schweinfurt, Schweinfurt, Germany

10Universitätsklinikum Erlangen, Erlangen, Germany

11Universität Köln, Zentrum familiärer Brust- und Eierstockkrebs, Köln, Germany

12Universitätsklinikum Ulm, Ulm, Germany

13Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, Berlin, Germany

14Universitätsklinikum Frankfurt, Frankfurt, Germany

15Institut für Pathologie UKGM, Universitätsklinikum Marburg, Marburg,

Germany

16Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg,

Germany

Purpose: is substudy compared the use of parenteral (IV) ferric car-

boxymaltose (FCM) with physician’s choice (PhCh) anaemia therapy in

breast cancer (BC) pts.

Methods: In GeparOcto trial pts with primary BC were randomized to

receive sequential, intensied, dose-dense epirubicin, paclitaxel, and cy-

clophosphamide (iddEPC) or weekly paclitaxel/liposomal doxorubicin

+/- carboplatin (PM(Cb))1. Pts with anaemia grade≥2 (haemoglobin

(Hb)<10g/dl), transferrin saturation (TSAT)≤20% and serum ferrit-

in<300ng/ml (amended to <600ng/ml) were randomized to receive week-

ly FCM or PhCh (no treatment, oral iron, erythropoiesis-stimulating

agent, or both) anaemia therapy. Stratication factors were CT arm (iddE-

PC vs PM(Cb)) and planned PhCh. Primary objective compared the rate

of pts achieving Hb≥11g/dl at 6 weeks (wks) of therapy between two arms.

Main secondary objectives were median time to achieve Hb≥11g/dl and

changes in iron parameters at baseline vs dierent time points.

Results: Less than anticipated pts had CT-induced anaemia. 125 pts were

randomized (62 in FCM, 63 in PhCh). Median age was 46 years (range 26-

66); median levels of Hb, serum ferritin and TSAT were 9.6 (7.6-11.8)g/

dl, 201 (3.0-551)ng/ml and 14.0% (4.0%-76.0%), respectively. Overall, 40

(32.0%) pts (22 in FCM and 18 in PhCh arm; p=0.447) reached Hb≥11g/

dl at 6 wks. Median time to achieve Hb≥11g/dl was 9.0 wks with FCM vs

10.6 wks by PhCh. Median Hb changes vs baseline were comparable in

both arms, while median serum ferritin and TSAT changes at earlier time

points were increased in FCM compared to PhCh.

Conclusions: is is the rst study investigating IV iron treatment for

dose-dense CT-induced anaemia in BC. 32% of pts reached Hb≥11g/dl at

6 wks, irrespective of anaemia therapy. FCM treatment increased ferritin

and TSAT levels but did not improve anaemia in comparison to PhCh in

this setting.

Reference:

1. Schneeweiss et al. Eur J Cancer 2019

Disclosure Statement: e anaemia supportive treatment substudy was nancially

supported by Vifor Pharma Ltd and the GeparOcto trial by Amgen, Roche and

Teva.

HT reported personal fees from Vofor, Roche, Amgen. CH reported personal fees

from Roche, Pzer Novartis, Celgene, Lilly, AstraZeneca outside the submitted

work. SL reported grant from Roche during the work and grants from Celgene,

Novartis, Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME, Daiichi Sankyo

outside of the submitted work, and patent EP14153692.0. CD reported stock

and other ownership interests from Sividon Diagnostics; honoraria from Teva,

Novartis, Pzer, Amgen; consulting or advisory role from MSD Oncology, Amgen,

Daiichi Sankyo and patents for VMScope digital pathology soware; patent appli-

cation EP18209672 - cancer immunotherapy; patent application EP20150702464

- therapy response. JH reported honoraria, consultancy or advisory role from Lilly,

Novartis, Roche, Pzer, Hexal, Astra Zeneca, MSD, Celgene, Abbvie; grants from

Novartis, Celgene and travel expenses from Roche, Pzer, Novartis, Celgene, Lilly.

AS reported grants from Celgene, Roche, AbbVie, Molecular Partner, personal fees

from Roche, AstraZeneca, Celgene, Pzer, AstraZeneca, Novartis, MSD, Tesaro,

Lilly outside the submitted work. PAF reported grants from Novartis, Biontech,

Novartis, Roche, Pzer, Celgene, Daiichi-Sankyo, Teva, Astra Zeneca, Merck

Sharp & Dohme, Myelo erapeutics, Macrogenics, Eisai, Puma and grants from

Cepheid, during the conduct of the study. VM reported personal fees from Amgen,

Celgene, Roche, Myelotherapeutics, Astra Zeneca, outside the submitted work.

KR reported personal fees from Tesaro, Astra Zeneca, Pzer outside the submitted

work. SS reported grants from Vifor; other from Amgen, Roche, Teva during the

conduct of the study; personal fees Amgen, Hexal, Roche, Mundipharma and oth-

er from Novartis outside the submitted work. TL reported non-nancial support

from AstraZeneca, Pzer, Pharma Mar, Daiichi Sankyo, Roche; personal fees from

MSD, Novartis, Teva, Tesaro. e other co-authors had nothing to disclose.

628

Analysis of ESR1 Mutations in Single Circulating Tumor

Cells from Metastatic Luminal Breast Cancer Patients Upon

Estrogen Deprivation Therapy

André Franken 1; Ellen Honisch 1; Florian Reinhardt 1;

Franziska Meier-Stiegen 1; Liwen Yang 1; Barbara Alberter 2;

Bernhard Polzer 2; Dieter Niederacher 1; Tanja Fehm 1; Hans Neubauer 1

1Department of Obstetrics and Gynecology, University Hospital and Medical

Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf, Deutschland

2Division “Personalized Tumor Therapy”, Fraunhofer Institute for Toxicology and

Experimental Medicine, Regensburg, Deutschland

Purpose: Mutations in the ligand-binding domain of the ESR1 gene are

frequently observed as a resistance mechanism against estrogen depriva-

tion therapy (EDT) such as aromatase inhibition in breast cancer patients.

Detection of such mutations oers the chance to optimize therapy strate-

gies. However, the predictive utility of the primary tumor for an acquired

resistance is limited and obtaining serial biopsies of metastatic lesions is

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challenging. To underline the application of a liquid biopsy, single circu-

lating tumor cells (CTCs) were analyzed with a next generation sequenc-

ing approach for the ESR1 coding region.

Methods: 132 CTCs from blood samples of 46 metastatic breast cancer

patients were analyzed. CTCs were enriched with the CellSearch® system,

isolated and genomic DNA was amplied. Furthermore, tumor tissue

samples from corresponding primary tumors and/or metastatic lesions

from patients with ESR1 mutations in CTCs were analyzed.

Results: ESR1 mutations were detected in CTCs from twelve of 46 pa-

tients exclusively in the patient group that was treated with EDT. No ESR1

mutations were found in CTCs from patients who received no or other ET

(p-value: 0.048). In seven patients mutations were detected in the hotspot

regions located in the ligand binding domain. Six novel mutations were

detected. ESR1 mutations were absent in primary tumor tissue samples of

patients with mutated CTCs.

Conclusions: Single cell CTC analysis for ESR1 mutations may be of clin-

ical value to identify patients who might progress under EDT and might

therefore benet from an early switch to an alternative ET or other treat-

ment regime.

636

Germline (G)BRCA1/2 Mutations (M) and Hematological

Toxicities in Patients (PTS) with Triple Negative Breast Cancer

(TNBC) Treated with Neoadjuvant Chemotherapy (NACT)

Jenny Furlanetto 1; Volker Möbus 2; Andreas Schneeweiss 3; Kerstin Rhiem 4;

Hans Tesch 5; Jens-Uwe Blohmer 6; Kristina Lübbe 7; Michael Untch 8;

Christoph Salat 9; Jens Huober 10; Peter Klare 11; Rita Schmutzler 4;

Fergus J. Couch 12; Bianca Lederer 1; Bernd Gerber 13; Dirk-Michael Zahm 14;

Ingo Bauerfeind 15; Valentina Nekljudova 1; Claus Hanusch 16;

Christian Jackisch 17; Theresa Link 18; Sibylle Loibl 1; Peter A. Fasching 19

1GBG, Neu-Isenburg, Germany

2Klinikum Frankfurt-Höchst, Frankfurt, Germany

3Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany

4Zentrum Familiärer Brust- und Eierstockkrebs, Uniklinik Köln, Köln, Germany

5Centrum für Hämatologie und Onkologie Bethanien Frankfurt, Frankfurt

Germany

6Brustzentrum Charité-Universitätsmedizin Berlin, Berlin, Germany

7DIAKOVERE Henriettenstift, Klinik für Gynäkologische Chirurgie, Senologie und

Onkologie, Hannover, Hannover, Germany

8HELIOS Klinikum Berlin Buch, Berlin, Germany

9Hämatologisch-Onkologische Schwerpunktpraxis Salat/Stötzer, München,

München, Germany

10Universitätsfrauenklinik Ulm, Ulm, Germany

11MediOnko-Institut GbR Berlin, Berlin, Germany

12Division of Experimental Pathology and Laboratory Medicine, Department of

Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

13Universitätsfrauenklinik am Klinikum Südstadt, Rostock, Rostock, Germany

14SRH Wald-Klinikum Gera, Gera, Germany

15Klinikum Landshut, Landshut, Germany

16Rotkreuzklinikum, München, München, Germany

17Sana-Klinikum, Oenbach, Oenbach, Germany

18Universitätsklinikum Dresden, Dersden, Germany

19University Hospital Erlangen, Erlangen, Germany

Purpose: BRCA1/2 plays a central role in DNA repair. Pts with gBRCA1/2m

treated with CT might be at higher risk of acute hematological toxicities

(hemtox) due to the lower level of functional BRCA1/2 protein. Published

results are discordant.

Methods: Pts with early TNBC and known gBRCA1/2m treated with an-

thracycline-taxane based NACT in the GeparQuinto (n=487), GeparSixto

(n=291) and GeparOcto (n=393) studies were included. Primary G-CSF

prophylaxis was foreseen only under iddETC in GeparOcto. Primary ob-

jective: rate of neutropenia grade (G)3-4 aer cycle 1 (C1); secondary ob-

jectives: rate of other hemtox G3-4, overall rate aer C1 and under taxane.

Results: 209/1171 pts (17.8%) had a gBRCA1/2m (177 gBRCA1m, 33

gBRCA2m). Median age was 48yrs [21-78]. e rate of neutropenia

G3-4 aer C1 in gBRCA1/2 wildtype (wt) vs gBRCA1/2m was 35.7% vs

37.4% (OR 1.08, 95%CI 0.78-1.48, p=0.658; multivariate analysis (MVA)

OR 1.26, 95%CI 0.87-1.82, p=0.226). No dierence was found in other

hemtox. gBRCA1/2 m status did also not predict for other hemtox G3-4

(OR 0.94, 95%CI 0.64-1.40, p=0.773; MVA OR 0.94, 95%CI 0.62-1.43,

p=0.779). No dierence was seen according to gBRCA1 or 2 m. Under tax-

ane, the rate of hemtox G3-4 in gBRCA1/2 wt vs gBRCA1/2m was 43.1%

(n=270) vs 59.5% (n=91) (OR 1.94, 95%CI 1.35-2.77, p<0.001; MVA OR

2.91, 95%CI 1.55-5.45, p=0.001); anemia G3-4 2.6% vs 3.3% p=0.584; leu-

copenia G3-4 32.7vs 47.1% p=0.001; neutropenia G3-4 35.8% vs 49.3%

p=0.003; thrombopenia G3-4 1.4% vs 4.6% p=0.024; febrile neutropenia

5.9% vs 4.6% p=0.696.

Discussion: We show that gBRCA1/2m are not associated with a signi-

cantly higher risk of severe hemtox. Under taxane, pts with gBRCA1/2m

demonstrate a higher rate of hemtox G3-4, especially neutropenia, com-

pared to wt pts.

Conclusions: Pts with gBRCA1/2m receiving taxane therapy should be

carefully monitored, being at higher risk for severe hemtox.

Disclosure Statement:

V. Möbus: AMGEN, Roche, Celgene, Myelotherapeutics, Astra Zeneca.

A. Schneeweiss: Celgene, Roche, AbbVie, Molecular Partner, Novartis,

AstraZeneca, MSD, Tesaro, Pzer, Lilly.

H. Tesch: Roche, Novartis.

K. Lübbe: Roche, Novartis, Genomic Health, Lilly.

M. Untch: Lilly Int., MSD Merck, Mundipharma, Myriad Genetics, Odonate,

Pzer GmbH, PUMA Biotechnology, Roche Pharma AG, Sano Aventis

Deutschland GmbH, TEVA Pharmaceuticals Ind Ltd, Novartis, Abbvie, Amgen

GmbH, Astra Zeneca, BMS, Celgene GmbH, Daiji Sankyo, Eisai GmbH, Lilly

Deutschland.

J. Huober: Novartis, Lilly, Roche, Pzer, Astra Zeneca, MSD, Celgene. C; A;

Lilly, Novartis, Roche, Pzer, Hexal, Astra Zeneca, MSD, Celgene. C; A; Celgene,

Novartis. O; A; Roche, Pzer, Novartis, Celgene, Daichi.

F.J. Couch: Qiagen, Ambry Genetics. O; A; AstraZeneca, GRAIL.

I. Bauerfeind: CELGENE, Roche.

C. Hanusch: Roche, Novartis, Lilly Pharma, Celgene, Astra Zeneca.

C. Jackisch: Roche, Amgen.

T. Link: Amgen, AstraZeneca, Pzer, Pharma Mar, Daiichi Sankyo, MSD,

Novartis, Teva, Tesaro, Roche.

S. Loibl: Patent EP14153692.0 pending. Roche, AbbVie, Amgen, AstraZeneca,

Celgene, Novartis,

Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME, Daiichi.

P.A. Fasching: Novartis, Biontech, Roche, Pzer, Celgene, Daiichi-Sankyo, TEVA,

Astra Zeneca, Merck Sharp & Dohme, Myelo erapeutics, Macrogenics, Eisai,

Puma, Cepheid.

e other co-authors had nothing to disclose.

657

Impact of Marging Shaving on Re-Excision Rates in Patients

with Primary Invasive Carcinoma and Carcinoma in Situ

InBreast Conserving Surgery. Data from a Population Based

Cohort of Clinical Cancer Registry

Miriam Fernandez-Pacheco 1; Ec Inwald 1; Michael Gerken 2;

Atanas Ignatov 1; Monika Klinkhammer-Schalke 2; Olaf Ortmann 1

1University Medical Center Regensburg. , Department of Gynaecology and

Obstetrics. , Regensburg, Deutschland

2Institute for Quality Management and Health Services Research, Tumor Center,

University of Regensburg , Regensburg, Deutschland

Purpose: Previous studies reported considerably high re‐excision rates

in breast‐conserving surgery (BCS) about 20%. Circumferencial Marging

Shaving (CMS) could be a surgical strategy to reduce re‐excision rates.

is study aimed to investigate the eects of CMS during BCS on reducing

residual tumor.

Methods: Totally, 440 patients with primary carcinoma or carcinoma in

situ of the breast who underwent BCS in the University Medical Center

Regensburg between 2017 and 2019 were analyzed. Patients who had CMS

or targeted re‐excision (TRE) depending on intraoperative mammogra-

phy or sonography were compared with patients receiving BCS without

removal of further tissue during primary surgery. e impact of these sur-

gical methods on residual tumor (R1) and further necessary intervention

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 23

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was analyzed by means of multivariable binary logistic regression model

adjusting for tumor size, nodal status, histologic al type, tumor biology,

neoadjuvant chemotherapy, surgeon, breast side, and patient´s age.

Results: A total of 306 patients had invasive‐ductal carcinoma. Of these,

40 patients received CMS, 82 TRE, and 184 no further excision. Aer

comparing these subgroups in a binary regression model there was a

tendency for CMS and TRE to have advantage over missing re‐excision

regarding residual tumor. Furthermore, aer adjusting for dierent vari-

ables, especially patients with T1‐tumors had a slightly signicant benet

from CMS.

Conclusions: Our results indicate a tendency that CMS reduces residual

tumor compared to TRE or to no further surgical action, although nal

results will be presented.

References:

1. Eect of cavity margin shavings to ensure completeness of excision on local re-

currence rates following breast conserving surgery. Barthelmes, L et al. Europ.

Journ. of Surg. Oncol., Vol. 29, Issue 8, 644 - 648

2. Systematic cavity shaving: Modications of breast cancer management and

long-term local recurrence, a multicentre study. Héquet, D. et al., Europ. Journ.

of Surg. Oncol., Vol. 39, Issue 8, 899 - 905

Disclosure Statement: e authors declare no conict of interest.

667

Pro and Contra Conversation: Vitamin D Deciency

and Cancer: Fact or Fiction?

André Robert Rotmann

Prof. Dr. Ingo Diel, Praxisklinik am Rosengarten, Mannheim, Deutschland

Vitamin D deciency and cancer Fact or ction?

It is undisputed that vitamin D is one of the central hormones of our body.

Likewise, vitamin D is needed to provide minerals like calcium for your

metabolism

making it indispensable for bone health.

Numerous studies show that vitamin D deciency is responsible for an

increased risk of developing common diseases such as diabetes, cardio-

vascular diseases, or even depression.

In addition, a link with the immune system and the development of can-

cer is postulated.

A current PUBMED search using the terms “vitamin D” and “cancer” re-

sulted in more than 10,000 hits!

e complementary and integrative oncologists are also increasingly con-

cerned with the possible consequences of vitamin D deciency and, ac-

cordingly, with substitution.

2 experts who deal with osteo-oncology will look at this exciting topic

with a pro and con discussion.

Prof. Ingo Diel from Mannheim is a proven, nationally and internationally

well-known osteo-oncologist and will take the contra position.

Dr. Andre Rotmann from Rodgau, gynaecologist-oncologist and actively

involved for years in the integrative and complementary medical treat-

ment of gynaecological tumours will take the pro position.

e discussion should be conducted based on the current status of science

and represent exciting and entertaining aspects of this current topic.

674

Breaking News from the Field of Complementary Oncology,

an Exiting Presentation of New Integrative Therapies in Breast

Cancer Patients

André Robert Rotmann

Rodgau, Rodgau, Deutschland

e aims of the integrative and complementary oncology is to minimalize

the side eects of the classic oncologic therapy including such as chemo-

therapy or antiendocrine therapy and above all to enhance life quality of

patients

ere is a great interest among patients worldwide in complementary on-

cological approaches.

e prognosis in the metastasing stage is unfortunately still poor

Curcumin is a plant-based substance known for thousands of years that is

seen as a promising substance in numerous preclinical studies, studies of

carcinoma cell lines and in animal research.

It has been reported to have a synergistic eect with a number of chemo-

therapeutic substances.

e aim of our randomised, double-blind, placebo-controlled study was

to demonstrate the ecacy of curcumin in combination with taxane in the

treatment of advanced breast cancer for the rst time

“Study of Ecacy of Curcumin in Combination with Chemotherapy in

Patients with advanced Breast Cancer: Randomized, Double Blind, Place-

bo Controlled Clinical Trial.”

150 patients with advanced breast cancer were randomly divided into two

groups of 75 each.

Group A were given paclitaxel with an intravenous placebo for a total of

12 weeks

Group B received curcumin 300 mg intravenously + paclitaxel q1w also

for 12 weeks

e aim of the study was to demonstrate the potential benets of curcum-

in administered intravenously in combination with paclitaxel compared

with the placebo and paclitaxel for patients with advanced breast cancer

e primary objectives were the ecacy of the combined treatment with

regard to the objective response rate (ORR), progression-free survival

(PFS), time-to-tumour progression (TTP), quality of life (QoL) as well as

the inuence of tumour markers

e secondary objectives were treatment safety and the observation of

possible side eects and disease progression

e exact design of the study and the dierentiated results were presented

and discussed for the rst time anywhere in the world at the 2019 German

Senology Congress in Berlin. is lecture was awarded high-ranking and

will be published soon

683

Cancer Management and Outcome of Young Patients (PTS)

with Breast Cancer (BC) Diagnosed at 40 Years (YRS) or

Younger

Sabine Seiler 1; Sabine Schmatloch 2; Mattea Reinisch 3; Tanja Neunhöer 4;

Marcus Schmidt 5; Christina Bechtner 6; Frederik Marmé 7;

Michael Wagner 8; Volker Möbus 9; Toralf Reimer 10; Anke Kleine-Tebbe 11;

Bruno Sinn 12; Elmar Stickeler 13; Michael Untch 14; Wolfgang Janni 15;

Fenja Seither 1; Sibylle Loibl 1

1GBG, Neu-Isenburg, Germany

2Brustzentrum, Elisabeth Krankenhaus Kassel, Kassel, Germany

3Brustzentrum, Kliniken Essen-Mitte, Essen, Germany

4Helios Dr. Horst Schmidt Kliniken, Wiesbaden, Wiesbaden, Germany

5Universitätsmedizin Mainz, Mainz, Germany

6Brustzentrum, Klinikum Memmingen, Memmingen, Germany

7Universitätsfrauenklinik Mannheim, Mannheim, Germany

8Siloah St. Trudpert Klinikum, Pforzheim, Pforzheim, Germany

9Klinik für Gynäkologie und Geburtshilfe, Klinikum Frankfurt Höchst, Frankfurt,

Germany

10Universitätsfrauenklinik und Poliklinik am Klinikum Südstadt Rostock, Rostock,

Germany

11Brustzentrum, DRK Kliniken Berlin, Berlin, Germany

12Institut für Pathologie, Charité - Universitätsmedizin Berlin, Berlin, Germany

13Uniklinik RWTH Aachen, Aachen, Germany

14HELIOS Klinikum Berlin Buch, Berlin, Germany

15Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany

Purpose: To provide data about modern BC treatment and oncological

outcome of young women aged ≤40 yrs.

Methods: e BC in pregnancy registry (BCP/GBG29) is a multicenter,

observational study that compares the management and outcome of BC

in pregnancy with non-pregnant pts ≤40 yrs as control cohort. All pts are

treated according to local standards. is analysis reports descriptively

baseline characteristics, BC therapy, short-term and long-term outcome

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of the young control cohort. Disease-free (DFS) and overall survival (OS)

rates were estimated using the Kaplan-Meier method.

Results: 964 non-pregnant women with a median follow-up of 38.7

months (95%CI 35.2-41.3) comprised the analysis set. Median age was 35

yrs (range 19-40). At diagnosis, 90.4% of pts had a stage T1-2 and 67.0%

were nodal negative; 42.7% had HR+/HER2- BC, 31.9% HER2+ BC and

25.4% triple-negative BC (TNBC). 3.2% of pts were M1 at primary di-

agnosis. 90.7% of pts with early BC (EBC) received chemotherapy (CT).

93.4% of pts with endocrine treatment for EBC received tamoxifen; there-

of 35.8 % with a GnRH analogue. Regardless of BC subtype, the high-

est pCR rates (ypT0 ypN0) were achieved in the cohort of pts age 18-29

yrs (HER2+ 47.8%, TNBC 65.2%, HR+/HER2-40.0%). e 3-yr DFS for

pts with EBC was 83.1% (95%CI 79.6%-86.0%) and the 3-yr OS 94.3%

(95%CI 91.9%-96.0%). e subgroup analysis per BC subtype suggested

a trend towards inferior DFS only in the group of pts ≤34 yrs and HR+/

HER2−BC (log rank p=0.058). 3.4% of pts got pregnant aer BC with a

median time from diagnosis to birth/termination of 3 yrs (range 2-7).

Conclusions: In this large cohort of young BC pts the reported treatments

reect the modern oncological management of these pts. e prognostic

relevance of young age by itself could not be shown for pts with HER2+

and TNBC. Yet, similar to previously reported results1 our data suggest a

trend towards inferior DFS in the group of pts ≤34 yrs and HR+/HER2−

BC.

Reference:

1. Loibl S, et al. Breast Cancer Res Treat. 2015

Disclosure Statement: SL reported grant from Roche during the work and grants

from Celgene, Novartis, Pzer, Roche, Seattle Genetics, Teva, Vifor, PRIME,

Daiichi Sankyo outside of the submitted work, and patent EP14153692.0. SS

reported consulting fees from Roche, Amgen, Novartis, Hexal. MR reported

personal fees and non-nancial support from Novartis , personal fees from Roche

, non-nancial support from Celgene , personal fees from Lilly , personal fees

from Astra Zeneca , personal fees and non-nancial support from Pzer, outside

the submitted work; MS reported grants and personal fees from Pierre-Fabre,

grants, personal fees and non-nancial support from Roche, grants, personal fees

and non-nancial support from Pzer, grants and personal fees from Novartis,

grants and personal fees from Astra-Zeneca, grants and personal fees from Eisai,

personal fees from Amgen, personal fees from Celgene, grants, personal fees and

non-nancial support from Pantarhei, grants and non-nancial support from

BioNTech, grants from Genentech, outside the submitted work; In addition, MS

has a patent EP2469440 (A3) Molecular markers for cancer prognosis pending,

a patent WO2009033941 (A1) A method for predicting the response of a tumor

in a patient suering from or at risk of developing recurrent gynecological cancer

towards a chemotherapeutic agent pending, and a patent WO2014118333 (A1)

Method for predicting the benet from inclusion a taxane in a chemotherapy

regimen in patients with breast cancer pending. FM reported personal fees and

non-nancial support from AstraZeneca, personal fees from Clovis, personal fees

from Tesaro, personal fees and non-nancial support from Roche, personal fees

and non-nancial support from Novartis, personal fees from AMGEN, personal

fees and non-nancial support from Pzer, personal fees from Curevac, personal

fees from Vaccibody, personal fees from PharmaMar, personal fees from Eisai,

personal fees from Celgene, personal fees from GenomicHealth, outside the sub-

mitted work; ES reported Travel Sponsoring from Roche and consulting fees from

Roche, Novartis, Pzer, Astra Zeneca. VM reported consulting fees from Amgen,

Roche, Tesaro, AstraZeneca and personal fees for advisory board from Amgen,

Roche, Myeloerapeutics.

e other co-authors had nothing to disclose.

694

A Randomized, Double-Blind, Phase III Trial of Neoadjuvant

Chemotherapy (NACT) with atezolizumab/Placebo in

Patients with Triple-Negative Breast Cancer (TNBC) Followed

by Adjuvant Continuation of atezolizumab/Placebo

(Gepardouze)

Sibylle Loibl 1; Christian Jackisch 2; Sabine Seiler 1; Priya Rastogi 3;

Jens Huober 4; Carsten Denkert 5; Andreas Schneeweiss 6; Claus Hanusch 7;

Peter A. Fasching 8; Jens-Uwe Blohmer 9; Michael Untch 10; Kerstin Rhiem 11;

Christine Solbach 12; Valentina Nekljudova 1; Joseph Costantino 3;

Norman Wolmark 13; Charles Geyer 14

1GBG, Neu-Isenburg, Germany

2Sana Klinikum Oenbach, Oenbach, Germany

3National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh,

University of Pittsburgh Cancer Institute School of Medicine, Pittsburg, USA

4Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm,

Germany

5Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum

Marburg, Marburg, Germany

6Nationales Centrum für Tumorerkrankungen, Heidelberg, Heidelberg, Germany

7Rotkreuzklinikum, München, München, Germany

8Universitätsklinikum Erlangen, Erlangen, Germany

9Gynäkologie mit Brustzentrum Charité-Universitätsmedizin, Berlin, Germany

10Helios Klinikum Berlin-Buch, Berlin, Germany

11Universität Köln, Zentrum familiärer Brust- und Eierstockkrebs, Köln, Germany

12Universitätsklinikum Frankfurt am Main, Frankfurt, Germany

13National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, UF

Health Cancer Center at Orland Health, Orlando, USA

14National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh,

Virginia Commonwealth University, Massey Cancer Center in Richmond,

Richmond, USA

Purpose: TNBC is associated with higher percentages of pathological

complete response (pCR) to NACT, and patients (pts) with a pCR have

a favorable prognosis. Pts with residual disease have a substantially

higher risk of recurrence than pts with other subtypes of breast cancer.1,2

erapeutic blockade of PD-L1 binding by atezolizumab has resulted in

relevant anti-tumor ecacy.3,4 e aim of GeparDouze is to determine

whether the addition of atezolizumab to NACT and adjuvant therapy

improves pCR and event free survival (EFS) in pts with TNBC.

Methods: GeparDouze (NSABP B-59/GBG96) is a phase III, double

blind, placebo-controlled trial. 1520 pts will be randomized (1:1) to

NACT + atezolizumab 1200mg or placebo IV every 3wks followed by ad-

juvant atezolizumab 1200mg or placebo IV for 6 months. Stratication

factors are Group (NSABP Foundation Inc.; GBG), tumor size (1.1-3.0cm;

>3.0cm), epirubicin or doxorubicin/cyclophosphamide schedule (q2w;

q3w), nodal status (positive; negative) and PD-L1 Status (positive; nega-

tive; indeterminate). Pts with primary cT1c-cT3 TNBC and centrally as-

sessed hormone receptor-status, HER2-status, and PD-L1-status on core

biopsy can be enrolled. Co-primary endpoints are pCR (ypT0/Tis ypN0)

and EFS. Main secondary endpoints are overall survival, recurrence-free

interval, distant disease-free survival, and toxicity.

Results: GeparDouze is an academic collaboration between NSABP and

GBG. So far, 357 patients are enrolled. It is expected that approximately

760 pts will be randomized within 34 months by NSABP sites and approx-

imately 760 patients by GBG sites.

Conclusions: GeparDouze will provide further data on ecacy and safety

of atezolizumab in pts with TNBC.

References:

1. Liedke C. J Clin Oncol. 2008.

2. Hahnen E. JAMA Oncol.2017.

3. Adams S. J Clin Oncol. 2016.

4. Schmid P. Cancer Res. 2017.

Disclosure Statement: e trial is nancially supported by Genentech/Roche.

SL reported grant from Roche during the work and grants from Pzer, Celgene,

Amgen, Novartis, AstraZeneca, Abbvie, Lilly, Daiichi Sankyo, Eirgenix outside of

the submitted work, and patent pending EP14153692.0. JC reported grants from

Genentech. CJ reported personal fees from Roche, Celgene during the conduct

of the study. CG reported grants from Genentech/Roche during the conduct of

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2018

the study; grants and non-nancial support from AstraZeneca, Abbvie, Genen-

tech/Roche; personal fees from Celgene outside the submitted work. SS reported

grants from Genentech/Roche during the conduct of the study. NW reported

other from Genentech/Roche during the conduct of the study. PR reported grants

from Genentech/Roche during the conduct of the study; other from AstraZeneca,

Genentech/Roche, Lilly outside the submitted work. CD reported shareholder

and cofounder from Sividon Diagnostics; honoraria/consultation from Teva,

Novartis, Pzer, Roche, Amgen, MSD, Daiichi Sankyo, Celgene, AstraZeneca;

atent application: EP18209672 – cancer immunotherapy. MU reported fee to the

institution from BMS, Lilly, PUMA Biotechnology; fee and non-nancial support

to the institution from Abbvie, Amgen, AstraZeneca, Celgene, Daiji Sankyo, Eisai

GmbH, Janssen Cilag, Johnsen&Johnsen, MSD Merck, Lilly, Mundipharma, Myri-

ad Genetics, Odonate, Pzer, Riemser, Roche, Sano Aventis Deutschland GmbH,

Sividon Diagnostics, TEVA Pharmaceuticals Ind Ltd outside the submitted work.

AS reported grants from Celgene, Roche, AbbVie, Molecular Partner, personal fees

from Roche, AstraZeneca Celgene, Roche, Celgene, Pzer, Novartis, MSD, Tesaro,

Lilly outside the submitted work. e other co-authors had nothing to disclose.

748

Predicting the Risk of Locoregional Recurrence after

Early Breast Cancer: an External Validation of the Dutch

Inuence-Nomogram with Clinical Cancer Registry Data

from Germany

Teresa Draeger 1, 2; Vinzenz Völkel 1, 2; Michael Gerken 2;

Monika Klinkhammer-Schalke 2; Sabine Siesling 3

1Caritas Krankenhaus St. Josef, Regensburg, Deutschland

2Tumorzentrum Regensburg, Regensburg, Deutschland

3Universität Twente, HTSR, Enschede, Niederlande

Purpose: Regular follow-up aer breast cancer treatment aims for ear-

ly detection of locoregional recurrences (LRR) to improve the patients’

outcome. By estimating individual 5-year recurrence-risks based on dif-

ferent patient- tumor- and treatment characteristics, the Dutch INFLU-

ENCE-nomogram can assist health professionals and patients in devel-

oping personalized risk-based follow-up pathways. e objective of this

study is to externally validate the INFLUENCE-nomogram on non-Dutch

patients.

Methods: Data derive from a large clinical cancer registry in southern

Germany, covering a population of 1.1 million. 6520 Patients with curative

resection of early-stage breast cancer, diagnosed between 2000 and 2012,

were included in the analysis. For every included patient, an individual

LRR-risk was estimated by the INFLUENCE-nomogram. Its predictive

ability was tested by comparing estimated and observed LRR-probabilities

using the Hosmer–Lemeshow goodness-of-t test and C-statistic based

on the receiver-operator-characteristic (ROC) curve.

Results: In the German validation-cohort, 2.8% of the patients developed

an LRR within 5 years aer primary surgery (n = 184). While the IN-

FLUENCE-nomogram generally underestimates the actual LRR-risk of

the German patients (p < 0.001), its discriminative ability is comparable

to the one observed in the original Dutch modeling-cohort (C-statistic

German validation-cohort: 0.73, CI 0.69–0.77 vs. C-statistic Dutch mod-

eling-cohort: 0.71, CI 0.69–0.73). Similar results were obtained in most

of the subgroup analyses stratied by age, type of surgery and intrinsic

biological subtypes.

Conclusions: e presented outcomes underline the generalizability of

the recently developed INFLUENCE-nomogram beyond the Dutch pop-

ulation. e model performance of INFLUENCE could be enhanced in

future by incorporating additional risk factors for LRR.

Funding: Funded by the Deutsche Forschungsgemeinscha (DFG, German

Research Foundation) – project number 417891978.

774

Predicting the Eectiveness of Sensor-Controlled Scalp

Cooling to Prevent Chemotherapy-Induced Alopecia in

Primary Breast Cancer Patients: It is the Regimen that Matters

Aila Ritter 2; A. Tabea Kurbacher 2; Susanne Herz 2; Nele Kettelhoit 2;

Gabriele Kolberg 2; Jutta A. Kurbacher 1; Claudia Schweitzer 2;

Christian M. Kurbacher 2

1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine

Gynäkologie und Geburtshilfe), Bonn

2Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:

Gynäkologische Onkologie), Bonn

Purpose: Sensor-controlled scalp cooling (SCSC) is now an accepted

means to prevent primary breast cancer (PBC) patients (pts) from chemo-

therapy (Ctx)-induced alopecia (CIA). is retrospective study sought to

determine pts who are most likely to benet from SCSC while being sub-

jected to CIA-inducing neoadjuvant (NACT) or adjuvant chemotherapy

(ACT) with anthracyclines (A), taxanes (T), or both.

Methods: 86 pts were included: NACT, 47 (54.6%); ACT, 39 (45.4%); dose-

dense (dd) Ctx, 38 (44.2%); non-dd Ctx 48 (55.8%); premenopausal, 48

(55.8%); postmenopausal, 38 (44.2%). Ctx regimens: A→T, 38 (44.2%),

T→A, 23 (26.7%), T, 25 (29.1%). CIA was quantied according to the Dean

score (DS). Data were analyzed regarding the SCSC completion rate, and

quality of hair preservation (success: DS 0-2, failure: DS 3-4). Moreover, the

following parameters were investigated in regard to the success of SCSC:

menopausal status, NACT vs ACT, dd Ctx vs non-dd Ctx, Ctx regimen.

Results: e success rate was 64.0% with 35 pts (40.7%) experiencing DS

0, and 20 (23.3%) showing DS 1-2. Eectiveness of SCSC did not dier for

most analyzed subgroups. e relative risk (RR) to experience CIA was 1.23

(CI: 0.87-1.74) for post- vs premenopausal pts, 1.07 (CI: 0.78-1.46) for ACT

vs NACT, 1.28 (CI: 0.91-1.80) for dd Ctx vs non-dd Ctx, and 1.556 (0.98-

2.36) for A+T vs T. However, the SCSC success rate for A→T (47.4%) was

signicantly lower (p = 0.016) as compared to T→A (73.9%) or T (80.0%).

Conclusions: SCSC was eective to prevent CIA in pts with PBC. All

therapeutic subgroups beneted from SCSC. A+T-based Ctx per se is not

a contraindication for SCSC. However, the success rate is signicantly

higher when the taxane precedes the anthracycline.

Disclosure Statement: All authors declare no conict of interests. t

775

The Aesthetic Results for Reconstruction After Oncoplastic

Breast Surgery

Anna Sukhotko; Aziz Zikiryahodjaev; Maria Ermoshenkova;

Artur Tukmakov

Moscow P.A. Gerzen’s Cancer Research Institute – The National Medical

Research Radiologic Center of the Ministry of Health of the Russian Federation,

Moscow, Russland

Purpose: To create of the new concept of surgical treatment as a compo-

nent of multi-therapy treatment of patients with breast cancers on postop-

erative quality of life (Qol).

Methods: We assessed 437 women who underwent breast conserving sur-

gery (BCS) or total mastectomy (TM) with immediate reconstruction in

P.A. Gertsen Moscow Research Institute from 2013 to 2018. Of the 437

patients, 290 (66,4%) had BCS,147( 33,6%) – skin-sparing mastectomy

(SSM). BCS included glandular reshaping (rotation ap, round-block

technique, batwing mastopexy, wise pattern-inverted T, vertical pattern).

Aer SSM, 7(4,7%) patients underwent immediate breast reconstruction

using a transverse rectum abdominis musculocutaneous (TRAM) ap,

47 (31,9%) - musculotoracodorsal (TDL) ap, 98 (66,7%) - musculolatis-

simus dorsi ap and it combination with endoprosthesis. A median fol-

low-up period was 58 months. Only 94 (21,5%) patients received adjuvant

polychemotherapy, combinations adjuvant polychemotherapy and radia-

tion therapy – 27 (6,1%) or endocrine therapy – 37(8,5%).

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Results: During a median follow-up period local recurrent were detected

at 30 (6,9%), distant metastasis – 65 (14,9%) patients. Overall disease-free

survival in patients with BCS stage I was 96,2%, IIA– 90%, IIB – 86,7%,

IIIA – 86,2% (р>0,05). Overall disease-free survival in patients with SSM

stage I was 92,9%, IIA– 91,2%, IIB – 84,4%, IIIA – 91,4% (р>0,05). e

postoperative cosmetic result aer BCS was assessed in 89,3% patients.

Conclusions: Oncoplastic surgery contributes is the better phychological

adaptation of patients. Variety of modications and options of reconstruc-

tive surgery causes problem of choice, which should be solved with patient

taking into account the clinical data. e extent of surgical intervention

does not aect the performance of the 5-year overall and recurrent surviv-

al and depends on the distribution process.

Reference:

1. Zork NM, et al. e eect of dedicated breast surgeons on the short-term

outcomes in breast cancer. Ann Surg. 2018;248(2):280-5.

Disclosure Statement: I agree

783

Surgical Resection of The Primary Tumor is Associated with

Increased Long-Term Survival in Patients with Stage IV

Breast Cancer

Anna Sukhotko; Aziz Zikiryahodjaev; Larisa Bolotina

Moscow P.A. Gerzen’s Cancer Research Institute – The National Medical

Research Radiologic Center of the Ministry of Health of the Russian Federation,

Moscow, Russland

Purpose: e problem of the treatment of disseminated breast cancer

(DBC) is specially urgent in the present situation, as there is no uniform

standard of care for these patients nowadays. Treatment of patients with

stage IV breast cancer is palliative, and, in some cases, symptomatic, so the

main task is to maximally prolong the life and improve its quality.

Methods: is investigation comparatively analyzed the results of com-

plex treatment with metastatic breast cancer. We analyzed retrospectively

treatment experience of 196 patients with generalized breast cancer in the

department of oncology and breast reconstructive surgery of P.A. Herzen

Moscow Cancer Research Institute from 2000 to 2018 Invasive ductul car-

cinoma was veried in128 patients (65,3%), invasive lobular carcinoma

- 33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving

drug and radiation therapies was performed in two patient groups. e

rst group includes 124 patients who underwent surgical intervention as

complex treatment, the second group includes 72 patients with only med-

ical therapy. Standard systemic therapy was given to all patients.

Results: Overall, 3-and 5-year survival in st group was 43,8 and 21%,

in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median

survival in patients with surgical treatment composed 32 month, in pa-

tients with only systemic therapy - 21. e factors having inuencing an

inuence on the prognosis and the quality of life outcomes for of patients

with generalized breast cancer were are also studied: hormone-dependent

tumor, Her2/neu hyper-expression, reproductive function status (age,

menopause existence).

Conclusions: Removing primary breast tumor in patients with general-

ized breast cancer improve long-term outcomes. ree- and ve-year sur-

vival increased by 28,7 and 16,3% respectively, and median survival – for

11 months. ese patients may benet from resection of the breast tumor.

One explanation for the eect of this resection is that reducing the tumor

load inuences metastatic growth.

Disclosure Statement: I agree

801

Transcriptional Factor KLF11 (Kruppel Like Factor 11)

As Potential Targets and a New Biomarker for the Prognosis

of Human Breast Cancer

LILI LIN; Kristina Pfender; Anna Hester; Udo Jeschke; Christina Kuhn

LMU Munich, University Hospital., Obsterics and Gynecology, München,

Deutschland

Purpose: is study aims to clarify prognostic impact of KLF11 in breast

cancer.

Methods:

1. We retrieved four independent investigation from ONCOMINE data-

base and investigate the prognostic signicance of KLF11 mRNA level

in patients with BC, by using the Kaplan-Meier Plotter online database.

2. We collected and analyzed the expression of KLF11 in 312 BC samples

by immunohistochemistry in our patients’ cohort and correlated its ex-

pression with several parameters and patient outcome.

Results: According to the meta-analysis across four ONCOMINE

datasets, we revealed KLF11 was one of the mostly down-regulated

genes in BC. Interestingly, also a meta-analysis from Kaplan-Meier

Plotter online database demonstrate that patients with KLF11 high

expression had signicantly shorter relapse free survival and distance

metastases free survival time than those with low expression. Moreover,

we performed our analysis to a patient cohort of 320 patients by using

immunohistochemistry and nally 312 patients KLF11 expression level

was obtained successfully. And we found that KLF11 high expression

in BC tissue sections is strongly associated with pT classication, ki67

expression level and molecular subtype grouped by Luminal A type and

Not Luminal A type. Importantly, patients with KLF11 low expression

had signicantly improved disease-free survival time than those with high

expression, which was consistent with KMP meta-analyses. In subgroups

of this whole cohort, signicantly highlight the same DFS trends in pT1,

pN0, tumor foci ≥2 , G2-G3 patients and patients without axillary lymph

node or contrast BC, also in ER positive, PR positive, Her2 negative, Ki67

expression less than 14% and in Luminal A BC patients. Cox proportional

hazard regression analysis further identied KLF11 as an independent

factor for poor prognosis.

Conclusions: Taken together, these observations rst strongly indicated

that KLF11 might be a cancer promoter for BC and a new biomarker for

the prognosis of human breast cancer.

Disclosure Statement: is study was funded by laboratory resources.

817

Experience of One-Stage Prepectoral Reconstruction

with Polyurethane-Coated Implants in Breast Cancer

Maria Vlasova 1; Eric Saribekyan 1; Aziz Zikiryakhodzhaev 1;

Anna Sukhotko 1; Irina Shirokich 1

1Department of Oncology and Reconstructive Breast and Skin Surgery, P.

Hertzen Moscow Oncology Research Institute – branch of the National Medical

Research Radiology Center, Ministry of Health of Russia, Moscow, Russia

Purpose: Results of one-stage prepectoral reconstruction with polyure-

thane-coated implants in breast cancer.

Methods: Since 2017 to 2019 in the Department of Oncology and Recon-

structive Breast and Skin Surgery P. Hertzen Moscow Oncology Research

Institute performed 207 one-stage prepectoral reconstruction with poly-

urethane-coated implants in breast cancer.

Results: We analyzed 97 patients, 59 (60,8%) of them received radiation

therapy. e follow-up period ranged from 3 months to 2 years. Radiation

therapy in terms of combined/complex treatment 1-2 months aer sur-

gery was performed in 42 (71,2%) patients, 6-8 months aer surgery (aer

adjuvant therapy) in 18 (30,5%) patients with breast cancer.

In this group the following complications were revealed: in 28 (25,77%)

patients seroma (over 30 days), the “red breast syndrome” - 25 (25,77%)

persons, the protrusion/extrusion of the prosthesis – 16 (16,5%), the mar-

ginal necrosis/necrosis – 5 (5,15%), the infectious complications - 4 (of

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4,12%), the rippling – 6 (6,18%). e capsular contracture III-IV degree

occurred in 10 patients (16,9 %) with radiation therapy, 8 (13,5%) cases

protrusion also during radiation therapy.

Conclusions: e prepectoral breast reconstruction with a polyurethane

coating implants can be applied as an alternative submuscular location,

because 80% of patients have a good aesthetic result. According to Breast

Q the quality of life of breast cancer patients is improving.

References:

1. Nahabedian M. Y. Innovations and advancements with prosthetic breast recon-

struction. - Breast J. 2018 Jul;24(4):586-591. 1 p.

2. De Vita R., Buccheri EM. et al. Breast Reconstruction Actualized in Nip-

ple-sparing Mastectomy and Direct-to-implant, Prepectoral Polyurethane

Positioning: Early Experience and Preliminary Results. - Clin Breast Cancer,

- 2019, - 1, 2, 8 p.

Disclosure Statement: I agree

829

Detection of Sentinel Lymph Nodes in Dierent Molecular

Subtype of Breast Cancer

Aziz Zikiryakhodzhaev 1, 2; Victor Efanov 1; Liudmila Kazaryan 1, 2;

Daria Bagdasarova 1; Ilona Duadze 1, 2

1P. Hertsen MORI (Moscow, Russia), P. Hertsen MORI (Moscow, Russia), Moscow,

Russland

2SBEO HPE “I. Sechenov First MSMU” of Ministry of Health , Moscow, Russland

Purpose: To analyze the frequency of lymph nodes metastasis in dierent

molecular biological types of breast cancer.

Methods: Surgical treatment of 485 women with primary operable (cT1-

2N0M0) invasive breast cancer (BC) and clinically negative regional

lymph nodes (LN) was performed from 12.2016 to 11.2018 in National

Medical Research Radiological Center of the Russian Federation. At the

rst stage all patients underwent breast conserving surgery or mastecto-

my; the status of regional LNs was examined using a sentinel lymph node

biopsy. e age of women ranged from 22 to 81 years. Based on the rec-

ommendations of St. Gallen Consensus (2013) patients were divided into

5 groups depending on the molecular biological type.

Results: Among 485 patients with primary operable breast cancer and

clinically negative regional LN, metastasis in sentinel LN were detected

in 115 (23.7%) (p<0,005) cases. Aer dividing patients into groups it was

found that metastasis in the SLN were veried in 55 (22%) (p<0,005) cases

with luminal type A, in 47 (29.3%) (p<0,005) cases with luminal type B,

Her2/neu-negative, in 5 (17.8%) (p<0,005) with luminal type B, Her2/neu

- positive, in 5 (17%) (p<0,005) with a triple negative type and in 3 (15.7%)

(p<0,005) cases with Her2/neu overexpressing breast cancer.

Conclusions: ere were found out that despite the aggressive course

and poor prognosis Her2/neu overexpressing and triple negative breast

cancer were less associated with metastasis in regional LNs in contrast to

other molecular biological types. However there is needed to make more

detailed research with a larger amount of material for an objective judg-

ment about the eect of the tumor molecular biology on lymphogenous

metastasis.

Reference:

1. Viale G., et al. Predicting the status of axillarysentinel lymph nodes in 4351

patients with invasive breast carcinomatreated in a single institution. Cancer

2005;103(3):492–500. DOI: 10.1002/cncr.20809.PMID: 15612028.

Disclosure Statement: No

835

Intrapericardial Chemotherapy for The Management of

Malignant Pericardial Eusion of a Metastatic Breast Cancer

Patient -A Case Report

Peter Ugocsai 1; Valeria Gerthofer 1; Florian Weber 2;

Michael Rechenmacher 3; Maria Hatzipanagiotou 1; Olaf Ortmann 1;

Stephan Seitz 1

1Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

2Institute of Pathology, University of Regensburg, Regensburg, Deutschland

3Department of Internal Medicine III, University Medical Center Regensburg,

Regensburg, Deutschland

Purpose: Malignant pericardial eusion with hemodynamic instability is

a life-threatening condition requiring an acute intervention. Breast cancer

(BC) is the second most common malignancy with pericardial metastasis.

Due to high relapse rates aer pericardiocentesis the therapy of choice

includes a temporary pericardial drainage and the application of a local

pericardial cytotoxic treatment.

Methods: Presentation of a 48-year old patient with the symptoms of

capsular brosis 2 years aer the primary therapy of a triple positive BC

(neoadjuvant CTH [TCH], unilateral mastectomy with axillary LND,

primary reconstruction with implant, adjuvant chest and axillary irra-

diation) under ongoing adjuvant HER2-targeted and endocrine therapy

with tamoxifen. Aer surgical resection of the brotic tissue a local re-

lapse was conrmed histologically (HR-positive/HER2-negative) without

signs of metastasis in CT scan. e endocrine therapy was modied to

letrozole and GnRH-analogue. e patient was presented within 3 weeks

with orthopnea, low oxygen saturation and tachycardia. In CT scan pleu-

ral, pericardial and mediastinal metastases were detected with pleural and

pericardial eusion, causing hemodynamic instability.

Results: e insertion of a subxiphoidal pericardial drainage was carried

out (cytology: TNBC) under intensive monitoring. 3 liters of pericardial

eusion was drained over 3 days along with the local application of mi-

toxantrone. We began a systemic monotherapy with epirubicin weekly.

A nearby complete remission of the pericardial metastasis was observed

along with stable disease of all other metastases over 12 weeks of therapy.

Conclusions: Individual therapy decisions are required in case of malig-

nant pericardial eusion. 80% of the cases are clinically stable without any

need for an invasive treatment. In case of hemodynamic instability mini-

mal invasive actions should be preferred to thoracic surgery. Due to high

relapse rates the local instillation of cytotoxic substances should also be

concerned.

Disclosure Statement: no conict of interest

847

KI67 Expression in Primary Male Breast Cancer

Melanie Erices-Leclercq 1; Christian Rudlowski 1; Stephan Baldus 2;

Frank Förster 3; Lars Schröder 4; Franziska Stiller 1

1Frauenklinik, Evangelisches Krankenhaus Bergisch Gladbach, Bergisch

Gladbach, Deutschland

2Institut für Pathologie, Zytologie & Molekularpathologie, Bergisch Gladbach,

Institut für Pathologie, Zytologie & Molekularpathologie, Bergisch Gladbach,

Bergisch Gladbach

3Praxis für Gynäkologie & Geburtshilfe: Gynäkologische Onkologie &

Palliativmedizin, MVZ Flemmingstraße Poliklinik Chemnitz, Chemnitz,

Deutschland

4Frauenlinik, Klinikum Hanau GmbH Klinik für Gynäkologie und Geburtshilfe,

Hanau, Deutschland

Purpose: Male breast cancer (MBC) is a rare disease. Approximately 1 %

of breast carinoma are diagnosed in men. Only few studies with small

patient numbers are available. Guidelines for diagnosis and treatment of

MBC are derived from female breast cancer. Both diseases share similar-

ities but there are signicant dierences regarding risk factors and prog-

nosis. In this study we evaluated the clinical signicance of proliferation

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factor Ki67 for MBC. e aim was to dene optimal Ki-67 scoring meth-

ods and cut-o values as prognostic marker for MBC.

Methods: Tumor tissue was obtained from 104 patients with primary

MBC. Clincopathologicial characteristics including follow-up data were

sampled and investigated. Ki67 expression was evaluated in paran-em-

bbeded specimen by using standard immunohistochemistry. We applied

three methods to analyse Ki67 expression: (1) Ki67 expression as percent-

age of nuclear Ki67 tumor staining on average (TA), (2) Ki67 expression

at the tumor border (TB) and (3) hotspots of Ki67 expression (HS). Sta-

tistical analysis was performed using receiver operating characteristics

(ROC) to determine specic cut o points for each method. Based on the

calculated cut o points, clinicopathological characteristics and overall

survival (OS) univariate and multivariate analysis as well as cox regression

were performed.

Results: Ki67 staining was successful in all cases. Ki67 expression cut o

points were 13.5 % for TA, 17.5 % for TB and 22.5 % for HS. Ki67 expres-

sion correlated with tumor size, nodal stage and tumor grading. All cut o

points were signicantly associated with OS. In multivariate analysis only

Ki67 TA and TB were statistically correlated to OS.

Conclusions: Ki67 expression measured by TA and TB are suitable to pro-

vide information regading OS in primary MBC. Patients with Ki67 less

than 13.5 % (TA) and 17.5 % (TB) showed signicant improved OS. Our

restrospective study illustrates Ki67 expression to be a promising prog-

nostic parameter in MBC.

Disclosure Statement: No disclosure

Cancer of Unknown Primary (CUP)

Cancer Prevention

Poster

Selection Bias in Observational Studies Evaluating Cancer

Screening Tests and Examinations

Jonas Czwikla 1; Ingo Langner 2; Ulrike Haug 2

1Universität Bremen, SOCIUM Forschungszentrum Ungleichheit und

Sozialpolitik, Bremen, Deutschland

2Leibniz-Institut für Präventionsforschung und Epidemiologie – BIPS, Bremen,

Deutschland

Purpose: We previously found that i) mammography screening partici-

pants and nonparticipants are not comparable in terms of 4-year all-cause

mortality, and ii) comorbidity measures determined based on claims data

are insucient to control for this selection bias [1]. We aimed to extend

these analyses to cervical, prostate, colorectal, and skin cancer screening.

Methods: Using claims data of the BARMER covering the years from 2007

to 2017, participants and nonparticipants of the Pap smear, digital rec-

tal exam, fecal occult blood test (FOBT)/colonoscopy, and visual whole-

body skin examination were identied. For each cancer screening, Cox

proportional hazards regression was used to compare all-cause mortality

between participants and nonparticipants within ≤ 7 years. We adjusted

for sex (if applicable), age (if applicable), residence, and comorbidity.

Results: Claims data of 5,765,852 persons were analyzed. e crude haz-

ard ratios (HRs) for death from any cause for participants vs. nonpar-

ticipants of the respective cancer screening were 0.22 (99.9% condence

interval 0.22-0.23) for Pap smear, 0.88 (0.86-0.89) for digital rectal exam,

0.51 (0.45-0.58) for FOBT/colonoscopy, and 0.70 (0.70-0.71) for skin ex-

amination. e adjusted HRs were 0.57 (0.56-0.58), 0.69 (0.68-0.70), 0.57

(0.50-0.65), and 0.75 (0.74-0.76), respectively.

Conclusions: Because cancer screening is expected to reduce all-cause

mortality by only 1-3% [2], the observed lower mortality among screening

participants must be due to selection bias. e extent of this bias diers

considerably between cancer screening tests and examinations. Obser-

vational studies evaluating the eectiveness of cancer screening need to

apply appropriate methods for controlling selection bias. Controlling only

for sex, age, residence, and comorbidity appears to be insucient.

References:

1. Czwikla J et al.: J Clin Epidemiol 2018;104:1-7.

2. Stang A et al.: Dtsch Arztebl Int 2018;115(29-30):481-6.

Disclosure Statement: No conict of interest.

339

Regional Disparities of Cancer Prevention – the Case

of Thuringia

Sebastian Henn 1; Jutta Hübner 2; Susann Schäfer 1; Anika Zorn 1

1Institut für Geographie, Friedrich-Schiller-Universität, Jena, Deutschland

2Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland

Purpose: It is a medically undisputed fact that physical activity, a healthy

nutrition and the minimization of risk factors (e.g. smoking, drinking)

form the three most important pillars of cancer prevention. Although

these factors are mainly determined by personal factors, there is no doubt

that regional infrastructures play an important role in cancer prevention.

Such infrastructures include facilities that address the above-mentioned

pillars through oering specialized services related to physical activity,

healthy eating or individual control of risk factors. Cancer prevention in-

frastructures vary considerably from one region to another; in particular,

signicant dierences can be expected between urban and rural areas.

is paper aims to compare the current state of regional cancer prevention

infrastructure on municipal level.

Methods: Methods of empirical social research (expert interviews,

semi-standardized surveys)

Results: Drawing on relevant statistics and other sources, we develop an

integrated indicator that combines information on the availability of pub-

lic and non-public prevention infrastructures, e.g. sports facilities, access

to regional unprocessed food and drug prevention services.

Conclusions: is indicator can serve as a basis for local actors to control

and further develop cancer prevention on a regional level. Although we

use the above indicator to characterize the current prevention infrastruc-

tures in uringia; the approach proposed can be applied to other regions

in Germany and/or abroad.

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382

Green Tea Extract Versus Placebo for the Prevention

of Colorectal Adenomas: a Randomized, Controlled

Trial - Miracle Trial

Stefan Menzler 1; Thomas Seuerlein 2; Helmut Messmann 3;

Gerhard Kleber 4; Alexander Zipprich 5; Stefanie Frank-Gleich 6; Hana

Algül 7; Klaus Metter 8; Frank Odemar 9; Theodor Heuer 10; Ulrich Hügle 11;

Rüdiger Behrens 12; Lukas Perkhofer 2; Catharina Scholl 13;

Katharina Schneider 13; Friederike Rohlmann 14; Rainer Muche 14;

Julia Stingl 15, 16; Thomas J. Ettrich 2

1Praxis Klinik Marburg, Marburg, Deutschland

2Ulm University Hospital, Department of Internal Medicine I, Ulm, Deutschland

3Augsburg University Hospital, Department of Internal Medicine III, Augsburg,

Deutschland

4Ostalb-Klinikum Aalen, Department of Internal Medicine I, Aalen, Deutschland

5Martin-Luther-University Halle-Wittenberg, Department of Internal Medicine I,

Halle (Saale)

6Private Practice Oncology, Halle (Saale), Deutschland

7Technical University Munich, Department of Internal Medicine I, München,

Deutschland

8Alb-Fils-Kliniken, Department of Gastroenterology, Göppingen, Deutschland

9Amos Klinikum Bernburg, Department of Internal Medicine, Bernburg (Saale)

Deutschland

10St. Bernhard-Hospital, Department of Internal Medicine I, Kamp-Lintfort,

Deutschland

11Krankenhaus Köln-Holweide, Department of Gastroenterology, Köln,

Deutschland

12Gastroenterologisch-onkologische Praxisklinik, Private Practice, Halle (Saale),

Deutschland

13Federal Institute of Drugs and Medical Devices, Research Division, Bonn,

Deutschland

14Ulm University, Institute of Epidemiology and Medical Biometry, Ulm,

Deutschland

15University of Bonn Medical School, Centre for Translational Medicine, Bonn,

Deutschland

16Federal Institute for Drugs and Medical Devices, Bonn, Deutschland

Purpose: Prevention of colorectal adenomas (CA) is likely to prevent col-

orectal cancer (CRC). Nutri- or chemoprevention of CRC is not yet es-

tablished. NSAIDs show some benet but also increase the bleeding risk.

Preclinical and small clinical trials suggest that epigallocatechingallate

(EGCG), a major polyphenol in green tea, has a good safety prole and

antineoplastic eects in the large bowel, but there are no data from large

trials. MIRACLE enrolled 1001 patients to examine the eect of a three

year intake of ECGC on the recurrence of CA aer polypectomy.

Methods: Double-blinded, placebo-controlled trial, 41 German centers,

recruitment 12/2011-6/2015. Patients aged 50-80 years who underwent

polypectomy within the last 6 months and tolerated EGCG well during a

one month run-in were randomized to standardized decaeinated EGCG

(150 mg bid) or placebo for 3 years. Primary endpoint: Incidence of CA

at the 3 year follow-up colonoscopy. Secondary endpoints: Occurrence,

number, localization, size, histological subtype of CA, frequency of CRC

and biomarker. Strata: Study center and low-dose aspirin (≤100 mg/d).

Results: Clinical parameters were well balanced. Primary endpoint was

analysed in the modied ITT set (modITT; n=309 patients in EGCG,

n=323 in placebo group giving informed consent and undergoing 3 year

follow up colonoscopy). n=102 patients in the EGCG and n=103 in the

placebo group were excluded due to missing follow up colonoscopy. In-

cidence of one or more CA aer 3 year of placebo or EGCG 150 mg bid

was 55.7 % and 51.1%, respectively (one sided adj. P=0.077, adj. RR 0.904)

in the modITT. In the PP-set constituting all modITT patients complet-

ing the study without major protocol violations the respective gures

were 54.3 % in the placebo and 48.3% in the EGCG group (one sided adj.

P=0.058, adj. RR 0.883). ere were no safety issues and no major dier-

ences in AEs between EGCG and placebo during the randomized phase.

Conclusions: 300 mg EGCG per day was well tolerated and showed a

trend towards a preventive eect on CA in the large bowel though not

statistically signicant.

432

Reduction of Genital Warts and Precancerous Lesions in HPV

Vaccinated Young Women in Bavaria

Sandra Fett 1; Martin Tauscher 1; Antonius Schneider 2; Stefanie Klug 3

1Kassenärztliche Vereinigung Bayerns (KVB)

2Institut für Allgemeinmedizin und Versorgungsforschung, , Klinikum Rechts der

Isar, Technische Universität München

3Lehrstuhl für Epidemiologie, Fakultät für Sport- und

Gesundheitswissenschaften, Technische Universität München

Purpose: HPV (Human Papillomavirus) vaccination has been available

in Germany since 2006 and was recommended by the Standing Commit-

tee on Vaccination (STIKO) in 2007 for girls and in 2018 for boys. e

vaccine should be given before the rst sexual contact in order to exclude

a prior exposure to the infection. e HPV vaccine is considered highly

eective and safe. Data from Australia, where vaccination rates are at 80%,

show a marked reduction in the rates of genital warts and precancerous

lesions of the cervix uteri in vaccinated young women. In Germany, 44.6%

of 17-year-old girls were fully vaccinated in 2015, while vaccination rates

were lower in Bavaria.

Methods: We assessed data of legally insured girls from the database of

the Bavarian Association of Statutory Health Insurance Physicians (KVB).

Vaccination coverage trends were evaluated cross-sectionally and longitu-

dinally. Age at vaccination and type of vaccine administered were inves-

tigated. Trends regarding diagnosis of genital warts (ICD-10: A63.0) and

precancerous lesions of the cervix uteri (ICD-10: N87.1, N87.2 and D06)

between vaccinated and unvaccinated young women were also evaluated.

Results: More than 350,000 girls were vaccinated against HPV in Ba-

varia from 2008 until 2018. e overall vaccination rate was 46.7%. In

2017, 51% of 18-year old girls were vaccinated at least once against HPV.

e number of pediatricians delivering vaccination showed a signicant

increase in comparison to gynecologists and general practitioners. e

vaccination rates increased signicantly over the years, but with strong

regional dierences within Bavaria. A reduction in genital warts as well

as precancerous lesions is already visible in young women who have been

vaccinated against HPV.

Conclusions: e rst evaluations on the use of HPV vaccine in Bavaria

show a promising decline in the diagnosis of genital warts and precan-

cerous lesions in vaccinated young women. However, a clear increase in

vaccination rates is necessary.

548

Hasco Study Protocol: Pilot Study for Systematic HPV

Self-Sampling for Non-Responders to the Cervical Cancer

Screening Program

Matthias Jentschke; Johanna Kampers; Peter Hillemanns

Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule

Hannover (MHH), Hannover, Deutschland

Purpose: In this pilot study we will evaluate a systematic approach to-

wards human papillomavirus (HPV) self-sampling for non-responders

to the German cervical cancer screening program. In 2020, an organized

screening program with co-testing (HPV test + cytology) in 3-yearly in-

tervals will be started. In the past, the participation rate was around 70%

in a time frame of three years. e non-participators are at higher risk to

develop cervical carcinoma. Previous studies have shown an improving

number of patients participating when being re-invited. e willingness to

participate in self sampling programs is even higher. Based on this infor-

mation, the Hannover Self-Collection study was designed to examine the

response rate and practicability of a systematic self-sampling approach.

Methods: 20.000 women aged 30 to 65 years living in the city and re-

gion of Hannover, Lower Saxony are randomly included. 10.000 women

directly receive a self-sampling kit, the other 10.000 a letter of informa-

tion and option to participate in the study (opt-out vs. opt-in strategy).

Stratications will be made by age (7 cohorts) and area of living (city vs

rural). Women tested positive for high-risk HPV (PCR-based HPV assay)

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are prompted to get a cytological smear by their gynecologist. Women

with normal cytology will be re-checked aer 6 months. Suspicious cy-

tology results lead to an immediate colposcopy. Further treatment will be

performed according to the German S3-guideline prevention of cervical

cancer.

Results: We designed a prospective randomized study to primarily exam-

ine: I) the participation rate (opt-out vs. opt-in model), II) the compliance

aer a positive HPV test, III) the comparison between two self-sampling

gadgets, IV) triaging the samples by new DNA-methylation tests.

Conclusions: To get hold of non-responders to cervical cancer screen-

ing programs; self-sampling for HPV is a promising option. Aim of this

study is to generate an overall recommendation to improve cervical can-

cer screening in Germany; especially for non-responders. is study is

supported by Deutsche Krebshilfe.

609

Protecting Young athletes from UV-Radiation – a Program

for Sports Schools

Friederike Stölzel 1; Michaela Wol 1; Vera Fieber 1; Melanie Glausch 1;

Eckhard Breitbart 2; Martin Bornhäuser 1, 3, 4; Nadja Seidel 1

1Universitätsklinikum Carl Gustav Carus, Universitäts Krebscentrum (UCC),

Dresden, Deutschland

2Arbeitsgemeinschaft Dermatologische Prävention (ADP) e. V., Hamburg,

Deutschland

3Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und

Poliklinik I, Dresden, Deutschland

4Nationales Centrum für Tumorerkrankungen (NCT), Dresden, Deutschland

Purpose: e incidence of melanoma and nonmelanoma skin cancer has

increased rapidly.1 Overexposure to ultraviolet radiation is an established

risk factor for the development of melanoma. Due to their intensive sun

exposure, student-athletes (SAs) performing outdoor sports have an

increased risk for developing skin cancer. 2 Using participatory program

planning (PPP), the authors developed a UV-protection-program (UPP)

that aims at supporting sports schools in establishing UV-protection

strategies.

Methods: To ensure feasibility, UPP was developed in 2019, closely coop-

erating with students (N=30), parents (N=5), teachers (N=8) and trainers

(N=7) of Sportgymnasium Neubrandenburg in 3 focus groups as well as

following WHO-recommendations for sun-protection at schools.

Results: In using PPP and working with focus groups-results, UPP could

be constructed to meet sports schools’ needs, for example employing di-

rective sun-protection briefs and including core values stated most fre-

quently by young athletes. UPP now consists of a project kit containing

videospots with tailored messages targeting students, trainers, teachers

and parents, as well as posters and a manual about sun-protection and

details on its successful implementation.

Conclusions: PPP has shown to be an eective and valuable method in

developing UPP for sports schools. Feasibility and acceptance of UPP will

be evaluated in September 2019 at Sportgymnasium and Sportoberschule

Dresden.

References:

1. Institut für Krebsepidemiologie e.V. (2018). Zahlen Zu Hautkrebs in Deutsch-

land.

2. Ally, M., et al. (2018). Promoting sunscreen use and sun-protective practices

in NCAA athletes: Impact of SUNSPORT educational intervention for

student-athletes, athletic trainers, and coaches. J Am Acad Dermatol, 78,

2:289-292.e2.

Disclosure Statement: No conicts of interest.

671

Update on HPV-attributable Cancer in Germany 2016

Nina Buttmann-Schweiger; Klaus Kraywinkel

Zentrum für Krebsregisterdaten (ZfKD), Robert Koch-Institut, Berlin,

Deutschland

Purpose: HPV-attributable cancer is a preventable disease. An estimat-

ed ~7.600 people in Germany were predicted to be diagnosed with an

HPV-attributable cancer1,2. e proportion of oropharyngeal (OP) squa-

mous cell carcinoma (SCC) was assumed to be relatively low (16-20%)

based on a pooled analysis of European study results. As country specic

results on the changing epidemiology of oropharyngeal (OP) squamous

cell carcinoma (SCC) in Germany is available3, our aim was to update pre-

vious estimates on the incidence of HPV-attributable cancer for Germany.

Methods: Nationwide cancer incidence on HPV-related SCC for 2016 was

calculated based on estimates of cancer incidence rates from the Center

for Cancer Registry Data for Germany. Proportions of cancers attributable

to HPV-infection (HPV-AF) were calculated according to previously pub-

lished methods2, taking new country specic results on HPV-prevalence

in OPSCC into account.

Results: Two clinical studies from Germany attribute >50% of most re-

cently diagnosed OPSCC to HPV (years of diagnosis 2013/2015). When

taking the country specic prevalence in OPSCC into account, the HPV-

AF in OPSCC will be more than twice as high as previously reported. e

total number of HPV-attributable cancer in Germany then approaches

10.000 new cases a year.

Conclusions: Previous estimates attributed a signicantly lower propor-

tion of OPSCC to HPV than most recent study results from two single

medical institutions in Germany suggest. Although the calculation of

HPV-related cancer burden remains methodologically challenging, recent

evidence indicates that oropharyngeal cancer increasingly contributes to

the burden of cancer. e HPV-AF for OPSCC in Germany will best be es-

timated by direct testing of HPV DNA/p16 overexpression/E6-E7 mRNA

expression in continuous representative sentinel sampling of tumor tissue

for monitoring the eects of HPV-vaccination in the German population.

References:

1. DOI: 10.3238/arztebl.2018.0586;

2. DOI 10.1186/s12885-017-3678-6;

3. DOI: 10.1002/cam4.2039

Disclosure Statement: no conicts of interest

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2018

Index

2018

814

Results of Intensied Breast Cancer Screening in Women

After Treatment for Hodgkin's Lymphoma in Childhood

and Adolescence

Kerstin Rhiem 1; Sarah Schott 2; Dorothee Speiser 3; Joke Tio 4;

Marion Kiechle 5; Susanne Briest 6; Anne-Sophie Vesper 7; Karin Kast 8;

Marion von Mackelenbergh 9; Elena Leinert 10; Christoph Engel 11;

Rita K Schmutzler 1

1Zentrum Familiärer Brust- und Eierstockkrebs, Centrum für Integrierte

Onkologie (CIO), Universitätsklinikum Köln, Köln, Deutschland

2Universitäts-Frauenklinik, Heidelberg, Deutschland

3Charite - Campus Mitte Klinik für Gynäkologie und Gynäkologische Onkologie

m.S. Laparoskopische Tumorchirurgie, Berlin, Deutschland

4Senologie, Universitätsklinikum Münster, Münster

5Klinik und Poliklinik für Frauenheilkunde, Technische Universitäts München,

München

6Brustzentrum, Universitätsklinikum Leipzig, Leipzig

7Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf

8Klinik und Poliklinik für Frauenheilkunde, Universitätsklinikum Dresden,

Dresden

9Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-

Holstein, Campus Kiel, Kiel

10Universitäts-Frauenklinik Ulm, Ulm

11Institut für Medizinische Informatik, Statistik und Epidemiologie,

Universitätsklinikum Leipzig, Leipzig

Purpose: Treatment of pediatric Hodgkin´s lymphoma (HD) by radio-/

chemotherapy lead to more than 90% survivors within at least 20 years.

However, patients suer from long-term sequelae particularly including

former radiation elds (e.g. secondary breast cancer/sBC). Since 2012 pa-

tients from HD studies (HD-78 to HD-95/Intervall) received the oer to

participate in the structured surveillance program for breast cancer (IFP)

within the German Consortium for Hereditary Breast and Ovarian Can-

cer (GC-HBOC).

Methods: We aimed to prospectively evaluate the ecacy of the iFE in fe-

male HD patients who had received radiation to the breast at young ages.

Within the “GPOH-HD-Spätfolgen” research project 534 women of a co-

hort study with more than 30 years´ follow up were still alive in 2012. 224

of them participated in the IFP.

Results: Median age at time of HD diagnosis was 16.3 years. By September

2019, 33 sBC had been diagnosed at a median age of 41.7y (range 26-56y).

Median Interval from HD to sBC was 23.4y. 22 prevalent (66.7%) and 11

incident (33.3%) cases of sBC were diagnosed. 10 of 11 (90%) incident

cases were detected in early stages (pTis/1a-c, pN0) while 8 of 22 (36.4%)

prevalent cases were diagnosed in stage pT2 and/or pN+ and one patient

was primarily metastasized. e majority of tumors were ductal invasive

(85%, n=22 von 26), G1-2 (72%, n=21 von 29) and hormone receptor pos-

itive (81%, n=25 von 31).

Conclusions: Women who received radiation to the breast for HD at

young ages face a signicantly elevated risk for sBC compared to risk-ad-

justed general population and should be informed about the IFP at the

centers of the GC-HBOC. In further studies we will investigate the role of

genetic risk factors in the pathogenesis of sBC.

Central Nervous System Tumors

Poster

126

Inhibition of the DNA Damage Response in Neuroblastoma

Cells Aects Sensitivity to Platinum Compounds

Katharina Roquette; Stefanie Gaertner; Gerhard Fritz

Institut für Toxikologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf,

Deutschland

Neuroblastoma (NB) are one of the most common malignant paediatric

brain tumors. Patients treated with aggressive platinum-based chemo-

therapy oen suer from long-term sequelae. Additionally, developed

drug resistance oen limits therapeutic ecacy. Here, we target the DNA

damage response (DDR) of NB cells diering in their N-myc status in or-

der to modulate their sensitivity to platinum compounds. Additionally, we

comparatively investigated the platinum compound response of NB cells

and cisplatin (CisPt) selected drug resistant NB variants. e DDR was

modulated by pharmacological inhibition of checkpoint kinases (CHK

1/2) and poly(ADP-ribose)-polymerase 1 (PARP 1) with LY2603618 or

Olaparib, respectively.

Cell viability was determined by using the Alamar Blue assay. Alterations

in cell cycle progression were assayed by ow cytometric analysis. e for-

mation of Pt-(GpG) intrastrand crosslinks was determined via Southwest-

ern blot. e amount of DNA double-strand breaks (DSBs) was quantied

by measuring the levels of nuclear γH2AX (S139 phosphorylated H2AX)

and 53BP1 foci via immunocytochemistry. Mechanisms of the DDR were

analysed by Western blot and the expression of CisPt-related susceptibili-

ty factors by quantitative realtime PCR.

N-myc amplied IMR-32 cells revealed an increased sensitivity to plati-

num compounds as well as to the pharmacological inhibitors in compari-

son to the N-myc nonamplied SH-SY5Y cells. Upon months-long CisPt

selection, CisPt resistant SH-SY5YR and IMR-32R variants were isolated,

which revealed up to 4-fold increased CisPt resistance as compared to

their corresponding wild-types. e resistant variants were cross-resistant

to carboplatin (CarboPt) as well as to LY2603618 and Olaparib. Pretreat-

ment with subtoxic concentrations of the inhibitors increased the sensitiv-

ity to CisPt in both cell lines.

Based on the data, we conclude, that pharmacological modulation of

the DDR/DNA repair is useful for targeting CisPt resistant NB cells

and, furthermore, to improve their responsiveness to platinum-based

chemotherapy.

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2018

Index

2018

282

Activity of Larotrectinib in TRK Fusion Cancer Patients with

Brain Metastases or Primary Central Nervous System Tumors

Serge Leyvraz 1; Alexander Drilon 2; Steven G Dubois 3; Anna F Farago 4;

Birgit Geoerger 5; Juneko E Grilley-Olson 6; David S Hong 7;

Davendra Sohal 8; Cornelis M van Tilburg 9; David S Ziegler 10; Nora C Ku 11;

Michael C Cox 11; Shivani Nanda 12; Barrett H Childs 12; Francois Doz 13

1Charité Comprehensive Cancer Center, Charité Berlin, Berlin, Deutschland

2Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College,

New York, United States

Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston,

United States

4Department of Medicine , Massachusetts General Hospital, Boston,

United States

5Gustave Roussy, Department of Pediatric and Adolescent Oncology,

Université Paris-Sud, Université Paris-Saclay, Villejuif, Frankreich

6University of North Carolina Hospitals, Chapel Hill, United States

7The University of Texas MD Anderson Cancer Center, Houston, United States

8Cleveland Clinic, Cleveland, United States

9Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University

Hospital and German Cancer Research Center (DKFZ), Heidelberg, Deutschland

10Sydney Children’s Hospital, Randwick, Australien

11Loxo Oncology, Inc., San Francisco, United States

12Bayer U.S. LLC, Whippany, United States

13Institut Curie, SIREDO Oncology Center (Care, Innovation and research for

children and AYA with cancer), Paris Descartes University, Paris, Frankreich

Purpose: TRK fusions are oncogenic drivers of a variety of cancers, many

of which can involve the central nervous system (CNS). Larotrectinib is

a FDA-approved selective TRK inhibitor for the treatment of TRK fusion

cancer. While larotrectinib has been shown to cross the blood–brain bar-

rier, its clinical activity in a series of TRK fusion cancers with primary or

metastatic intracranial disease has not been described.

Methods: Patients (pts) with non-primary CNS solid tumors with brain metas-

tases, or primary CNS tumors harboring a TRK fusion treated with larotrectinib

in two clinical trials (NCT02637687, NCT02576431) were identied. Larotrec-

tinib was administered until disease progression, withdrawal, or unacceptable

toxicity. Disease status was investigator-assessed (RANO, RECIST).

Results: 24 pts were identied: 6 non-primary CNS solid tumors (4 lung

cancer, 2 thyroid cancer; fusion type: 2 ETV6-NTRK3, 2 SQSTM1-NTRK3,

1 EPS15-NTRK1; 1 TPR-NTRK1; age range 25–79 y) and 18 primary CNS

tumors (6 glioblastoma, 4 glioma, 3 glioneuronal, 3 NOS, 2 astrocytoma;

13 fusion genes involving NTRK2, and 2 each NTRK1 and NTRK1; aged

2–79 y). In 5 pts with non-primary CNS tumors evaluable for response,

the best objective response to therapy was PR in 3 (60%, 1 pending conr-

mation), SD in 1 (20%). Duration of response ranged from 9+ to 13 mo. In

the 18 pts with primary CNS tumors, the best overall response to therapy

was CR in 2 pts, PR in 3 pts, for an objective response rate of 36%. 9 pts

(64%) had SD. Disease control ≥ 24 w was seen in 10 pts (71%). Duration

of treatment ranged from 0.03+ – 16.6+ mo.

Conclusions: Larotrectinib is active in pts with TRK fusion cancers with

intracranial disease. Conrmed responses and durable disease control were

seen in metastatic disease and primary CNS tumors of various histologies.

ese results further support expanded testing for TRK fusions across all

cancers, including primary CNS tumors.

sion. is abstract was accepted and previously presented at the 2019 Asco

Disclosure Statement:

Serge Leyvraz reports personal fees from Immunocore, and Bayer outside the

submitted work.

Alexander Drilon reports HONORARIA/ADVISORY BOARDS: Ignyta/

Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP erapeutics,

AstraZeneca, Pzer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui

erapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health; ASSOCIATED

RESEARCH PAID TO INSTITUTION: Pzer, Exelixis, GlaxoSmithKlein, Teva,

Taiho, PharmaMar; RESEARCH: Foundation Medicine; ROYALTIES: Wolters

Kluwer; OTHER: Merck - Food/Beverage, Puma - Food/Beverage, and CME

HONORARIA: Medscape, OncLive, PeerVoice, Physicians Education Resources,

Targeted Oncology, Research to Practice.

Steven G. DuBois reports Loxo: consultancy and travel expenses, and Roche:

travel expenses.

Anna F. Farago reports Research support ‒ Bayer Healthcare, Loxo Oncology,

Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,

Merck, Ignyta, Amgen, Novartis; Consultant ‒ Bayer Healthcare, Loxo Oncology,

Inc., Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, PharmaMar,

Boehringer Ingelheim, and Honorarium – Dava Oncology, Clinical Care Options,

Medical Learning.

Birgit Geoerger none.

Juneko E. Grilley-Olson none.

David S. Hong reports Research/Grant Funding: AbbVie, Adaptimmune, Amgen,

Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate erapeutics, Genentech,

Genmab, Ignyta, Innity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati,

MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pzer, Seattle

Genetics, Takeda; Travel, Accommodations, Expenses: LOXO, MiRNA, ASCO,

AACR, SITC, Genmab; Consulting or Advisory Role: Alpha Insights, Axiom,

Adaptimmune, Baxter, Bayer, Genentech, Glg, Group H, Guidepoint Global,

Innity, Janssen, Merrimack, Medscape, Numab, Pzer, Seattle Genetics, Takeda,

Trieza erapeutics, and Other ownership interests: Molecular Match (Advisor),

OncoResponse (founder), Presagia Inc (Advisor).

Davendra Sohal reports Consulting advisory role, Perthera, Ability Pharma;

Honoraria, Foundation Medicine, and Research funding, Novartis, Cellgene,

OncoMed, Bayer, Genentech, Bristol-Myers Squibb, Agios, Incyte, Loxo.

Cornelis M. van Tilburg reports Bayer: advisor, and Novartis: advisor.

David S. Ziegler nothing to disclose.

Nora C. Ku is an employee of Loxo Oncology Inc.

Michael C. Cox was an employee of Loxo Oncology Inc.

Shivani Nanda is an employee of Bayer.

Barrett H. Childs is an employee of Bayer.

Francois Doz reports BAYER: travel expenses, advisory board, and ROCHE:

advisory board.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 33

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2018

Index

2018

386

Targetable FGFR3 Fusions and Novel FGFR3 Mutations

in Glioma

Jens Schittenhelm 1, 2, 3; Lukas Ziegler 2; Michel Mittelbronn 4, 5, 6, 7;

David Capper 8; Isabel Burghardt 1, 9; Antti Poso 10, 11; Saskia Biskup 12;

Marko Skardelly 1, 9, 13; Ghazaleh Tabatabai 1, 3, 9

1Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,

University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

2Department of Neuropathology, Institute of Pathology and Neuropathology,

University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

3German Consortium for Translational Cancer Research (DKTK), DKFZ partner

site Tuebingen, Tuebingen, Deutschland

4Luxembourg Centre of Neuropathology (LCNP), Dudelange, Luxemburg

5Centre for Systems Biomedicine (LCSB), University of Luxembourg,

Esch-sur-Alzette, Luxemburg

6National Center of Pathology (NCP), Laboratoire National de Santé (LNS),

Dudelange, Luxemburg

7Department of Oncology (DONC), Luxembourg Institute of Health (LIH),

Luxembourg, Luxemburg

8Institute for Neuropathology, Charite, Berlin, Deutschland

9Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain

Research, Tuebingen, Deutschland

10Department of Internal Medicine VIII, University Hospital of Tuebingen,

Eberhard Karls University Tuebingen, Tuebingen, Deutschland

11School of Pharmacy, University of Eastern Finland, Kuopio, Finnland

12CeGaT GmbH and Praxis für Humangenetik, Tuebingen, Deutschland

13Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls

University Tuebingen, Tuebingen, Deutschland

Purpose: Fibroblast growth factor receptor (FGFR) inhibitors are cur-

rently in clinical development. A subset of IDH wildtype glioblastomas

contain fusion genes between FGFR3 and transforming acidic coiled-coil

protein 3 (TACC3). e resulting increase in FGFR3 expression is con-

sidered as a marker to detect FGFR3 fusions in gliomas. e aim of the

present study was (i) to investigate alterations in FGFR3 in the Tübingen

glioma cohort and (ii) to evaluate the role of FGFR3 immunohistochem-

istry in addition to targeted NGS gene panel sequencing and RT-PCR.

Methods: FGFR 3 immunohistochemistry (IHC) screening was carried

out in 548 glioma samples using tissue microarrays. e results were val-

idated in external cohorts with a total of 326 patients. RT-PCR screen-

ing and IHC was performed in 101 consecutive sampled glioblastomas

to determine the frequency of FGFR3 –TACC3 fusions. Further targeted

NGS panel sequencing was carried out in 74 samples. e eect of a novel

specic mutation was further studied by molecular modelling.

Results: e spectrum of molecular alterations that we detected included

FGFR3 fusions, FGFR3 amplication and FGFR3 gene mutations. FGFR3

fusions were associated with strong FGFR3 protein expression and dis-

tinct histological patterns. Molecular modelling of the novel mutation

suggests that this molecular event leads to an activating FGFR3 kinase

function. A detailed analysis will be presented.

Conclusions: Gliomas may carry more than one FGFR3 alteration in

the same tumor. FGFR3 IHC might be a useful marker to identify FG-

FR3-TACC3 fusions in IDH-wildtype tumors and could thus be further

included in the regular IHC diagnostic algorithm to detect therapeutic

targets.

Disclosure Statement: GT served on Advisory Boards of BMS, MSD and AbbVie;

received research and/or travel grants from Roche Diagnostics, Novocure and

Medac, received speakers` fees from Medac, Novocure.

400

Personalized Medicine for Neuro-Oncology Patients:

Implementation and Outcome of the Molecular Tumor

Board Tuebingen

Isabel Burghardt 1, 2, 3; Patrick Strohmaier 2, 3; Mirjam Renovanz 1, 2, 3;

Jens Schittenhelm 1, 3, 4; Kirsten Wyrwich 2; Kristina Ruhm 3; Janina Beha 3;

Yvonne Möller 3; Özner Önur 3; Saskia Biskup 5; Cristiana Roggia 6;

Michael Bitzer 3, 7; Marcos Tatagiba 1, 2, 3; Daniel Zips 3, 8; Nisar Malek 3, 7;

Ghazaleh Tabatabai 1, 2, 3

1Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,

University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

2Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain

Research, Tuebingen, Deutschland

3Center for Personalized Medicine, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

4Department of Neuropathology, Institute of Pathology and Neuropathology,

University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

5CeGaT GmbH and Praxis für Humangenetik, Tuebingen, Deutschland

6Institute of Medical Genetics and Applied Genomics, University Hospital of

Tuebingen, Eberhard Karls University of Tuebingen, Tuebingen, Deutschland

7Department of Internal Medicine I, University Hospital of Tuebingen, Eberhard

Karls University Tuebingen, Tuebingen, Deutschland

8Department of Radiation Oncology, University Hospital of Tuebingen, Eberhard

Karls University Tuebingen, Tuebingen, Deutschland

Purpose: e Molecular Tumor Board (MTB) at the University Hospital

Tuebingen has been established in 2016 to discuss molecular data-driv-

en personalized therapeutic strategies for all tumor patients. e current

study aims at retrospectively reviewing the MTB experience so far for

neuro-oncology patients with a particular focus on feasibility, work ows

for molecular diagnostics, review of frequent molecular patterns and clin-

ical outcome.

Methods: Medical records from MTB neuro-oncology patients from

April 2016 – August 2019 were reviewed. e retrospective study was ap-

proved by the ethical board. We discussed molecular proling reports in

the MTB, evaluated the evidence for actionability of molecular alterations

and recommended molecular data-driven therapeutic strategies.

Results: So far, around 300 neuro-oncology patients with dierent his-

tological entities (primary and metastatic tumors) were presented in the

MTB. Molecular diagnostics included gene panel sequencing, transcrip-

tome analysis and immunohistochemical staining of associated targets in

selected cases. Actionable alterations were frequently detected. A precise

analysis will be presented. In the subgroup of glioblastoma patients, mo-

lecular alterations in the CDKN2A/2B and in the PTEN gene occurred

frequently. Immunohistochemical evaluation of associated targets was

included with antibodies detecting relevant downstream targets. Genetic

changes and protein data in the associated cellular pathways will be cor-

related. e nal analysis of therapeutic strategies and clinical outcome

data will be presented.

Conclusions: A personalized medicine program is feasible for neuro-on-

cology patients, particularly in the absence of further treatment options or

matching clinical trials. e MTB ensures an appropriate interdisciplinary

discussion of tumor molecular proles, therapeutic decisions and docu-

mentation of outcome.

Disclosure Statement: GT: served on Advisory Boards of BMS, MSD, AbbVie;

research and/or travel grants: Roche, Novocure, Medac, speakers` fee: Medac,

Novocure.

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2018

Index

2018

402

Ecacy of Entrectinib in Patients (PTS) with Solid Tumors and

Central Nervous System (CNS) Metastases: Integrated Analysis

from 3 Clinical Trials

Tobias Overbeck 1; Salvatore Siena 2, 3; Robert C. Doebele 4; Alice T. Shaw 5;

Christos C. Karapetis 6, 7; Daniel S.W. Tan 8; Byoung Chul Cho 9;

Dong-Wan Kim 10; Myung-Ju Ahn 11; Matthew G. Krebs 12, 13; Koichi Goto 14;

Pilar Garrido 15, 16; Anna F. Farago 5; Herbert H.F. Loong 17; Diego Tosi 18;

Minal Barve 19; Brian P. Simmons 20; Chenglin Ye 20; Xinhui Huang 20;

Alexander Drilon 21

1University of Göttingen, Department of Hematology and Medical Oncology

and Lungentumorzentrum Universität Göttingen, Göttingen

2Grande Ospedale Metropolitano Niguarda, Niguarda Cancer Center, Milan,

Italien

3Università degli Studi di Milano, Department of Oncology and Hemato-

Oncology, Milan, Italien

4University of Colorado, Aurora, CO, United States

5Massachusetts General Hospital Cancer Center, Boston, MA, United States

6Flinders Medical Centre, Adelaide, Australien

7Flinders University, Adelaide, Australien

8National Cancer Centre Singapore, Division of Medical Oncology, Singapore,

Singapore

9Yonsei Cancer Center, Division of Medical Oncology, Seoul, South Korea

10Seoul National University Hospital, Department of Internal Medicine, Seoul,

South Korea

11Samsung Medical Center, Sungkyunkwan University School of Medicine,

Division of Hematology-Oncology, Department of Medicine, Seoul, South Korea

12The University of Manchester, Division of Cancer Sciences, Manchester, United

Kingdom

13The Christie NHS Foundation Trust, Experimental Cancer Medicine Team,

Manchester, United Kingdom

14National Cancer Center Hospital East, Kashiwa, Japan

15Ramón y Cajal University Hospital, Madrid, Spanien

16Universidad Alcalá, Madrid, Spanien

17The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin,

Hong Kong

18Institut du Cancer de Montpellier Inserm U1194, Montpellier University,

Medical Oncology Department, Montpellier, Frankreich

19Mary Crowley Cancer Research Center, Dallas, TX, United States

20Genentech, Inc., South San Francisco, CA, United States

21Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, Division

of Solid Tumor Oncology, Department of Medicine, New York, NY, United States

Purpose: Entrectinib potently inhibits kinases encoded by the NTRK and

ROS1 genes. It attains therapeutic levels in the CNS with antitumor activ-

ity in intracranial tumor models. We report integrated data (31/05/18 cut-

o) from 3 Phase 1/2 entrectinib trials (ALKA-372-001, EudraCT 2012-

000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267) in

adults with ROS1 fusion-positive NSCLC (ROS1+) or NTRK fusion-posi-

tive solid tumors (NTRK+), with/without baseline CNS metastases.

Methods: Pts had locally advanced/metastatic NTRK+ or ROS1+ tumors

by nucleic acid-based conrmation. CNS metastases were detected by CT/

MRI. Tumor assessments by blinded independent central review (RECIST

v1.1): wk 4, then every 8 wks. Primary endpoints: objective response rate

(ORR), duration of response (DOR). Secondary endpoints: clinical bene-

t rate (CBR), PFS, OS, intracranial ecacy and safety.

Results: Most pts had ≥1 prior therapy; 33% had baseline CNS metas-

tases. Outcomes for ROS1+ NSCLC (n=53) and NTRK+ solid tumors

(n=54; 24% sarcoma, 18% NSCLC) ecacy evaluable pts by baseline CNS

disease (no v yes) were:

ROS1+ (n=30 v 23):

% ORR (95% CI): 80.0 (61.4, 92.3) v 73.9 (51.6, 89.8)

CR, n (%): 3 (10.0) v 0

PR, n (%): 21 (70.0) v 17 (73.9)

mDOR, mo (95% CI): 24.6 (11.4, 34.8) v 12.6 (6.5, not evaluable [NE])

% CBR (95% CI): 80.0 (61.4, 92.3) v 73.9 (51.6, 89.8)

mPFS, mo (95% CI): 26.3 (15.7, 36.6) v 13.6 (4.5, NE)

mOS, mo (95% CI): NE v NE (10.5, NE)

Intracranial % ORR; mDOR; mPFS: NE v 55.0 (31.5, 76.9; n=20); 12.9

(5.6, NE); 7.7 (3.8, 19.3)

NTRK+ (n=42 v 12):

% ORR: 59.5 (43.3, 74.4) v 50.0 (21.1, 78.9)

CR: 4 (9.5) v 0

PR: 21 (50.0) v 6 (50.0)

mDOR: 12.9 (7.1, NE) v NE (4.2, NE)

% CBR: 61.9 (45.6, 76.4) v 75.0 (42.8, 94.5)

mPFS: 12.0 (8.7, 15.7) v 7.7 (4.7, NE)

mOS: 20.9 (16.8, NE) v 14.3 (51, NE)

Intracranial % ORR; mDOR; mPFS: NE v 54.5 (23.4, 83.3; n=11);

NE (5.0, NE); 14.3 (5.1, NE)

Entrectinib was tolerable with a manageable safety prole; most

treatment-related AEs were grade 1–2.

Conclusions: Entrectinib induced clinically meaningful durable respons-

es in pts with ROS1+ NSCLC or NTRK+ solid tumors with/without CNS

disease.

Conicts of Interest:

Tobias Overbeck: Honoraria (self) from AstraZeneca, BMS, BoehringerIngelheim,

Eli Lilly, Medac, MSD, Novartis, Roche/Genentech; Advisory/Consultancy for

AstraZeneca, BMS, BoehringerIngelheim, Eli Lilly, Medac, MSD, Novartis,

Roche/Genentech; Research grant/Funding (institution) from AstraZeneca, Eli

Lilly, Roche/Genentech, Sano-Aventis; Travel/Accommodation/Expenses from

AstraZeneca, Boehringer-Ingelheim, Eli Lilly, and Roche/Genentech.

Salvatore Siena: Advisory board member for Amgen, Bayer, BMS, CheckmAb,

Celgene, Clovis, Daiichi-Sankyo, Incyte, Merck, Novartis, Roche/Genentech, and

Seattle Genetics.

Robert C. Doebele: Honoraria from Genentech/Roche, Takeda/Millenium; Advi-

sory board for Genentech/Roche, Rain erapeutics; Travel reimbursement from

Genentech/Roche, Ignyta; Licensing fees for biological materials from Genentech/

Roche, Ignyta, Foundation Medicine, Loxo Oncology; Consulting for Ignyta, Loxo

Oncology, Bayer, Rain erapeutics; Sponsored research for Ignyta, Loxo Oncol-

ogy; Stock ownership at Rain erapeutics; Licensing fees from patent from Rain

erapeutics, and Abbott Molecular.

Alice T. Shaw: Consulting, honoraria, and institutional (research) support from

Genentech, Roche, and Ignyta.

Christos C. Karapetis: Advisory board role for Roche, MSD, BMS, Amgen, Astra-

Zeneca, Eisai; Honoraria from Roche, Eisai, and AstraZeneca.

Daniel S.W. Tan: Honararia (self) from Merck, Pzer, Novartis, Boehringer

Ingelheim, Roche, Takeda; Advisory / Consultancy for Novartis, Bayer, Boeh-

ringer Ingelheim, Celgene, Astra Zeneca, Eli-lily, Loxo; Research grant / Funding

(self) from Novartis, Astra Zeneca, GlaxoSmithKline, Bayer, Pzer; Travel /

Accommodations / Expenses from Merck, Pzer, Novartis, Boehringer Ingelheim,

Roche,Takeda.

Byoung Chul Cho: Research funding from Novartis, Bayer, AstraZeneca,

MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono

Pharmaceuticals, Dizal Pharma, MSD; Consulting role for Novartis, AstraZeneca,

BoehringerIngelheim, Roche, Bms, Ono Pharmaceuticals, Yuhan, Pzer, Eli Lilly,

Janssen, Takeda, MSD; Stock ownership at eraCanVac Inc., Gencurix, Inc.,

Bridge Biotherapeutics; Royalty from Champions Oncology.

Dong-Wan Kim: Research funding (institution) from Alpha Biopharma, Astra-

Zeneca/MedImmune, Hanmi, Janssen, Merus, Mirati erapeutics,Inc, MSD,

Novartis, Ono Pharmaceutical, Pzer, Roche/Genentech, Takeda, TP erapeutics,

Xcovery, and Yuhan.

Myung-Ju Ahn: Advisory / Consultancy for AstraZencea, Lilly, MSD, Takeda,

Alpha pharmaceuticals, Roche, Yuhan.

Matthew G. Krebs: Advisory Boards for Roche, Janssen, OCTIMET Oncology,

Achilles erapeutics; Travel grants from AstraZeneca, BerGenBio; Research fund-

ing from Roche.

Koichi Goto: Honoraria (institution) from MSD, AstraZeneca, Novartis Pharma,

LifeTechnologies Japan, Pzer Japan Inc., Bristol-Myers Squibb., Ono Pharma-

ceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd,

Eli Lilly Japan, Nippon Boehringer lngelheim Co., Ltd, Takeda Pharmaceutical

Co., Ltd, Otsuka Pharmaceutical, Kyowa Hakko Kirin Co.,Ltd; Research grant/

Funding (institution) from Taiho Pharmaceutical Co., Ltd, Chugai Pharmaceuti-

cal Co., Ltd, Ono Pharmaceutical Co., Ltd, Astra Zeneka, Sumitomo Dainippon

Pharma Co., Ltd, Bristol-Myers Squibb, MSD, Astellas Pharma Inc., Eisai Co., Ltd,

DAIICHI SANKYO Co., Ltd, Pzer Inc., Kyowa Hakko Kirin Co., Ltd, Novartis

Pharma, Takeda Pharmaceutical Co., Ltd, Eli Lilly Japan, Merck Serono Co., Ltd,

Ignyta,Inc., Boehringer Ingelheim Japan, Inc., Janssen Pharmaceutical, Ignyta,

Inc., Loxo Oncology, Sysmex Corporation Xcoo, Inc., and Medical & Biological

Laboratories Co., Ltd.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 35

Inhalt

2018

Index

2018

Pilar Garrido: Consulting and advisory services (self) for Roche, MSD, BMS,

Boehringer Ingelheim, Pzer, AbbVie, Guardant Health, Novartis, Eli Lilly,

AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaking, public pre-

sentations (self) from Takeda, AstraZeneca, Roche, MSD, BMS, Pzer, Novartis,

Boehringer Ingelheim, Gilead Sciences, Rovi; Financial support for clinical trials

(institution) from Roche, MSD, BMS, Takeda, Eli Lilly, Pzer, Novartis, Phar-

mamar, Celgene, Sano, Gsk, eradex Oncology, Blueprint Medicines; Financial

support for contracted research (institution) from Guardant Health, and Sysmex.

Anna F. Farago: Advisory/Consultancy for Roche, Genentech, Loxo Oncology,

Bayer, Pharmamar, AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingel-

heim; Research grant/Funding (self) from AbbVie, AstraZeneca; Research grant/

Funding (institution) from AbbVie, and AstraZeneca, Pharmamar, Merck, Bris-

tol-Myers Squibb, Amgen, Genentech/Roche, Ignyta, Loxo, Bayer, Novartis; Travel/

Accommodation/Expenses from Roche, Genentech, Loxo, Bayer, Pharmamar,

AstraZeneca, Bristol-Myers Squibb, AbbVie, and Boehringer Ingelheim.

Herbert H.F. Loong: Consulting or advisory role (self) for GlaxoSmithKline,

Roche/Genentech, Novartis; Speakers’ Bureau (self) for AbbVie, Ignyta, Novartis;

Research Funding (institution) from MSD Oncology; Travel/Accommodation/

Expenses from Roche, MSD Oncology, Bayer, and Pzer.

Diego Tosi: Travel expenses for scientic meetings from Pzer, Astellas, MSD;

Research funding from Janssen, Astellas, Ipsen; Research contract from Phosplatin

erapeutics; Research grant from Ipsen.

Minal Barve: No conicts of interest to disclose.

Brian P. Simmons: Employment at Genentech, Inc.; Stock ownership at Roche.

Chenglin Ye: Employment at Genentech, Inc.; Stock ownership at Roche.

Xinhui Huang: Employment at Genentech, Inc.; Stock ownership at Roche.

Alexander Drilon: Honoraria or advisory boards for Ignyta/Genentech/Roche,

Loxo/Bayer/Eli Lilly, Takeda/Ariad/Millenium, TP erapeutics, AstraZeneca,

Pzer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui erapeu-

tics, Exelixis, Tyra Biosciences, VerastemOncology, MORE Health, AbbVie;

Associated research paid to institution: Pzer, Exelixis, GlaxoSmithKline, Teva

Pharmaceutical Industries, Taiho Pharmaceutical Co., Ltd, Pharmamar; Research

for Foundation Medicine; Royalties from Wolters Kluwer; Food and beverage from

Merck, Puma; CME Honoraria from Medscape, OncLive, PeerVoice, Physicians’

Education Resources, Targeted Oncology, Research to Practice, Oncology.

All authors: Medical writing and editorial support for the original abstract was

provided by Gardiner-Caldwell Communications, Asheld Healthcare Commu-

nications and sponsored by Roche in accordance with Good Publication Practice

guidelines. Support for third-party editing assistance for this abstract, furnished

by Helen Singleton, PhD, Sammi Cham, BA, and Niamh Gould, BA, of Health

Interactions, was provided by Roche Pharma AG. is study was funded by

F. Homann La-Roche, Basel, Switzerland.

407

Regorafenib in Advanced High Grade Glioma

Irina Gepfner-Tuma 1, 2; Theophilos Tzaridis 3, 4; Ulrich Herrlinger 3;

Ghazaleh Tabatabai 1, 2

1Interdisciplinary Division of Neurooncology, Hertie-Institute for Clinical Brain

Research, Tuebingen, Deutschland

2Center for CNS Tumors, Comprehensive Cancer Center Tuebingen-Stuttgart,

University Hospital of Tuebingen, Eberhard Karls University of Tuebingen,

Tuebingen, Deutschland

3Division of Neuro-Oncology, Department of Neurology and Center of

Integrated Oncology, University Hospital Bonn, Bonn, Deutschland

4Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital

Bonn, Bonn, Deutschland

Purpose: e REGOMA phase II trial has recently reported an overall

survival benet of the oral multikinase inhibitor regorafenib in progres-

sive glioblastoma1. We analyzed retrospectively the clinical ecacy of re-

gorafenib and treatment-related adverse events in a series of patients with

advanced stages of glioma.

Methods: Patients with progressive glioma received 80-160 mg rego-

rafenib daily (3 weeks on, 1 week o) until tumor progression or dose-lim-

iting toxicity.

Results: We treated 24 patients with regorafenib (21 glioblastoma, 1 as-

trocytoma, 1 midline glioma, 1 oligodendroglioma). Median progres-

sion-free survival was 2.1 months, median overall survival 4.1 months.

e occurrence of hand-foot-syndrome correlated with longer median

survival. Adverse events of CTCAE grades 1-3 included fatigue (13/24,

54%), dermatological toxicity (8/24, 33%), increased lipase (5/24, 21%)

and endocrinological events (4/24, 17%). One patient developed a treat-

able corticosteroid-responsive aseptic meningitis during regorafenib.

Conclusions: In the absence of further available treatment strategies, re-

gorafenib could be evaluated as an option in progressive glioblastoma2.

Dermatological toxicity might be useful as a clinical marker for patient

stratication and could be investigated in future prospective trials. Given

the broad application of regorafenib beyond the eld of neuro-oncology,

the occurrence of a treatable aseptic meningitis3 might be of interest for

the general clinical management during regorafenib treatment.

References:

1. Lombardi et al., Lancet Oncol 2019

2. Tzaridis et al., Neuro Oncol 2019

3. Gepfner-Tuma et al., Neuro Oncol Practice 2019

Disclosure Statement: IG-T: speaker’s fees from Novocure; grant from Medac.

UH: grants and personal fees from Roche; personal fees and nonnancial support

from Medac; personal fees from Novocure; Novartis; Daichi Sankyo; Riemser;

Noxxon; Abbvie; Bayer. GT served on Advisory Boards of BMS; MSD; AbbVie;

received research and/or travel grants from Roche; Novocure; Medac; speaker’s

fees from Medac; Novocure.

438

TargetingofCSF1R and PD1 in Experimental Glioma

Justyna M. Przystal 1, 2, 3; Hannes Becker 1, 3; Denis Canjuga 1; Carola H. Ries 4;

Martina Schmittnaegel 4; Nataliya Korinetska 1; Marilin Koch 1;

Jens Schittenhelm 2, 3, 5; Marcos Tatagiba 1, 3; Susanne C. Beck 1;

Ghazaleh Tabatabai 1, 2, 3

1Hertie Institute for Clinical Brain Research, Interdisciplinary Division of Neuro-

Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen,

Tübingen, Deutschland

2German Translational Cancer Consortium (DKTK), DKFZ partner site Tübingen,

Tübingen, Deutschland

3Comprehensive Cancer Center Tübingen-Stuttgart, Center for Neuro-Oncology,

University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen,

Deutschland

4Roche Innovation Center Munich, Oncology Division, Roche Pharmaceutical

Research and Early Development, Penzberg, Deutschland

5Institute for Neuropathology, University Hospital Tübingen, Tübingen,

Deutschland

Purpose: Glioblastoma is an aggressive primary tumor of the central ner-

vous system. e median overall survival of patients is in the range of 1.5

years even in selected clinical trial populations investigating multimodal

therapies. Novel therapeutic strategies are urgently needed. erapeutic

targeting of the glioblastoma-associated microenvironment is a promis-

ing approach in this regard. Particularly macrophages represent a highly

abundant population of tumor-inltrating host cells. e colony stimulat-

ing factor-1/colony stimulating factor-1 receptor (CSF1/CSF1R) axis plays

an important role for macrophage dierentiation and survival.

Methods: To assess CSF1R in human glioblastoma, we performed CSF1R

staining in human tissue samples from primary and recurrent glioblasto-

ma. For targeting the tumor microenvironment (TME) we performed an

anti-CSF1R approach in experimental glioma using the antibody clone

2G21 syngeneic preclinical glioma mouse models. TME-associated treat-

ment patterns were evaluated by histology and immunochemistry.

Results: CSF1R is present in human samples of primary and recurrent

glioblastoma. Monotherapy with anti-CSF1R antibody increased latency

until the onset of neurological symptoms in SMA560-bearing VM/Dk

mice and CD204 and CD11b positive cells were reduced suggestive aer

treatment. A combination of anti-PD1 and anti-CSF1R antibodies further

prolonged the symptom-free survival and led to higher CD8+/CD4+ ratios

in vivo.

Conclusions: Our results identify CSF1R as a promising therapeutic tar-

get for glioblastoma, probably in combination with PD1 inhibition.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts36

Inhalt

2018

Index

2018

Reference:

1. Ries, C. H., et al. (2014). “Targeting tumor-associated macrophages with

anti-CSF-1R antibody reveals a strategy for cancer therapy.” Cancer Cell 25(6):

846-859

Disclosure Statement: HB received funds from a Siegmund Kiener doctoral

fellowship. GT received grants from Roche Diagnostics. GT received research

and/or travel grants from Roche, Novocure, Medac; speakers` fees from Medac,

Novocure.

454

Argyrin F Leads to Targetable Treatment-Induced

Vulnerabilities in Experimental Glioma

Bianca Walter 1; Denis Canjuga 1; Michael Ghosh 2; Susanne C. Beck 1;

Przemyslaw Bozko 3; Stefan Stevanovic 2; Nisar Malek 3;

Ghazaleh Tabatabai 1

1Hertie Institute for Clinical Brain Research , Interdisciplinary Division of Neuro-

Oncology, University Hospital Tübingen, Eberhard Karls University Tübingen,

Tübingen, Deutschland

2Interfaculty Institute for Cell Biology, Department of Immunology, University of

Tübingen, Tübingen, Deutschland

3Department of Internal Medicine I, University Hospital Tübingen, Eberhard

Karls University Tübingen, Tübingen, Deutschland

Purpose: Glioblastoma is an aggressive primary tumor of the nervous

system with limited ecient treatment options. e proteasome inhibi-

tor Argyrin A and its recently developed analogue Argyrin F display an-

ti-tumor activity [1, 2]. Proteasome inhibition is a promising therapeutic

strategy in glioma. In fact, the EORTC 1709 trial investigates Marizomib

in newly diagnosed glioblastoma. We consequently aimed at exploring the

anti-glioma activity of Argyrin F in experimental glioma to evaluate its

suitability for further clinical development in glioblastoma.

Methods: We performed an in-depth characterization of Argyrin F in-

duced eects in LN229, LNZ308, SMA560, and GL261 cell lines by acute

cytotoxicity (24 h and 48 h) and clonogenicity assays. We determined

p27KIP1 levels by immunoblot, proteasome activity by uorometry, and cell

cycle progression by ow cytometry. We investigated the HLA ligandome

with an EC20 dosage and conducted in vivo treatments in the syngeneic

SMA560/VMDk glioma model.

Results: We observed treatment-related reductions of proteasome activi-

ty, cell viability and clonogenic survival (> 50% reduction at 0.5 mg/mL)

and an increase of p27KIP1 levels. Argyrin F induces the presentation of im-

munogenic peptides on the cell surface. In vivo analysis and histological

characterizations are ongoing and will be presented.

Conclusions: Argyrin F has anti-glioma activity and might, therefore, be

an interesting therapeutic approach for clinical translation in glioblasto-

ma, potentially in combination with immunotherapeutic strategies.

References:

1. Chen X et al, Cancer letters 2017

2. Nickeleit I et al, Cancer Cell 2008

Disclosure Statement: GT served on Advisory Boards of BMS; MSD and AbbVie;

received research and/or travel grants from Roche Diagnostics; Novocure and

Medac; received speaker’s fees from Medac; Novocure.

492

The Inuence of an Infection with S. Aureus on Growth and

Cytokine Secretion of Glioblastoma Multiforme (GBM)

Claudia Lemke 1; Susanne Grube 1; Lorena Tuchscherr 2; Rolf Kal 1;

Jan Walter 1, 3

1Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland

2Institut für Medizinische Mikrobiologie, Universitätsklinikum Jena, Jena,

Deutschland

3Klinik für Neurochirurgie, Klinikum Saarbrücken, Saarbrücken, Deutschland

Purpose: e relationship between postoperative infections and a pro-

longed survival in patients with GBM remains controversial. Neverthe-

less, there are no studies on the inuence of infections of GBM cells on

survival and proliferation of these cells. ere is evidence to suggest that

pathogens may stimulate the tumor cells to secret cytokines. To test these

hypotheses, we established an in vitro infection model with Staphylococ-

cus aureus.

Methods: Four primary GBM cultures and one culture of human brain

astrocytes (HBA) were infected with the strain 6850 of S. aureus and ob-

served for 7 days. At dierent timepoints the number of intracellular bac-

teria was determined. A gene expression analysis was performed by qPCR

and the secretion of proinammatory cytokines (IL6, IL8) was measured

by ELISA.

Results: All cell cultures expressed factors to enable bacterial internal-

ization and were infectable with S. aureus. e GBM cells ingested up

to 4.7% of the bacteria, the HBA up to 0.3%. e HBA eliminated the

bacteria very quickly and survived better than the GBM, but also the

GBM showed a quick elimination and recovered. ere was a signi-

cant increase (p<0.01) in expression of the proliferation markers MKI67

(6.7fold), PLK1 (2.9fold) and the transcription factor c-Jun (3.0fold) in

all infected GBM cells, compared to uninfected cells. 24h aer infection,

there was an increase in secretion of the proinammatory cytokines IL6

(7.2fold, p<0.001) and IL8 (1.8fold) in the GBM cells, compared to unin-

fected cells. e HBA also showed an increase in IL6 and IL8 secretion,

but to a lower extent (IL6: 5.6fold, IL8: 1.1fold). Interestingly, the unin-

fected HBA showed a signicantly higher IL6 (up to 10.2fold) secretion

than the uninfected GBM cells.

Conclusions: In summary, both GBM and HBA could be infected by S.

aureus, whereby the GBM proved to be more vulnerable to the infection.

Furthermore, there was an increased secretion of proinammatory cyto-

kines in GBM, comparable to uninfected HBA, indicating a stimulation

of the GBM cells.

Disclosure Statement: ere are no conicts of interest.

506

Radiotherapy for Glioblastoma – Feasibility, Results and

Correlation of Target Volumes and Location of Relapse in a

Monoinstitutional Sample

Christoph Süß 1; Rüdiger Schenk 2; Felix Steger 1; Elisabeth Bumes 3;

Oliver Kölbl 1; Matthias Hautmann 1

1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg

2Klinik für Innere Medizin, St. Elisabeth-Krankenhaus, Essen

3Klinik und Poliklinik für Neurologie der Universität Regensburg,

Bezirksklinikum Regensburg, Regensburg

Purpose: Glioblastoma is the most common primary brain tumor. Radio-

therapy is a well-established adjuvant treatment modality. However, near-

ly all patients suer from a relapse of the tumor. e aim of this survey was

to document the feasibility and results and to correlate the location of the

relapse with the target volumes and isodoses.

Methods: All patients, which received RT or RCT at the University Hospi-

tal Regensburg for glioblastoma from 2004 to 2012 were included.

94 patients could be identied. e median age was 57 years with 60.6%

male and 39.4% female patients. For 30 patients we could perform a fu-

sion of the MRI scan showing the relapse with the treatment plans and

correlate the localization.

e median follow-up was 16 months (IQR 9 to 24 months).

Results: e feasibility of radiotherapy was good.

e median overall survival was 14 months. Aer 12 months 62% and

aer 24 months 20% of the patients were alive.

e median progression free survival was 8 months. Aer 6 months 40%,

aer 12 months 75% and aer 24 months 93% suered from a tumor

relapse.

In most of the cases the main volume of the recurrent tumor occurred

within the initial high dose area (60 Gy). Only one recurrent glioblastoma

was completely outside the initial target volumes.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 37

Inhalt

2018

Index

2018

Conclusions: e feasibility of radiotherapy was good, but the survival

data are still unsatisfying. e main challenge is the avoidance of local

relapse inside the target volumes.

Disclosure Statement: On behalf of all authors, the corresponding author declares

that there are no conicts of interest.

514

Inhibiting BHLH Transcriptional Networks Using Dominant

Negative E47 Leads to a Strong Anti-Glioma Activity in Vitro

and in Vivo

Marilin Koch 1, 2; Stefan Czemmel 3; Felix Lennartz 2, 4; Sarah Beyeler 1, 2;

Justyna Pryztal 1, 2; Parameswari Govindarajan 1, 2; Denis Canjuga 1, 2;

Manfred Neumann 1, 2; Patrizia Rizzu 5; Marcos Tatagiba 6; S Rajaraman1, 2;

Sven Nahnsen 3; Peter Heutink 5; Olivier Raineteau 7; Ghazaleh Tabatabai 2, 4

1Interdisziplinäre Sektion Neuroonkologie, Klinik und Poliklinik für Neurologie,

Universitätsklinikum Tübingen, Eberhard-Karls-Universität Tübingen, Tübingen,

Deutschland

2Hertie-Institut für klinische Hirnforschung, Tübingen, Deutschland

3Zentrum für Quantitative Biologie (QBiC), Eberhard-Karls-Universität Tübingen,

Tübingen, Deutschland

4Interdisziplinäre Sektion Neuroonkologie, Klinik und Poliklinik für Neurologie,

Klinik für Neurochirurgie, Universitätsklinikum Tübingen, Eberhard-Karls-

Universität Tübingen, Tübingen, Deutschland

5Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Tübingen,

Deutschland

6Interdisziplinäre Sektion Neuroonkologie, Klinik für Neurochirurgie,

Universitätsklinikum Tübingen, Eberhard-Karls-Universität Tübingen, Tübingen,

Deutschland

7Inserm, Stem Cell and Brain Research Institute, Université de Lyon, Bron,

Frankreich

Inhibiting bHLH transcriptional networks using dominant negative

E47 leads to a strong anti-glioma activity in vitro and in vivo

Purpose: e transcription factor E47 forms heterodimers with he-

lix-loop-helix (HLH)/basic helix-loop-helix (bHLH) proteins such as

ID-1 and Olig2, both of which are frequently overexpressed in gliomas.

e dominant negative variant of E47 (dnE47) lacks a nuclear transloca-

tion signal and eventually leads to sequestration of HLH and bHLH fac-

tors into the cytoplasm. In this study, we investigated a combination of

this approach with standard of care (SOC) temozolomide and irradiation

to explore its therapeutic ecacy and molecular mechanisms.

Methods: Doxycycline-inducible dnE47 lentivirus was used to transduce

long-term and stem cell glioma cell lines. In vitro experiments including

immunoblots, immunocytochemistry stainings, cytotoxicity and clono-

genic assays were performed for functional evaluation of the dnE47 ap-

proach. Eects upon latency of symptom onset were investigated in vivo.

CAGE and RNA-seq were used to study transcriptional changes upon

dnE47 induction.

Results: dnE47 induction led to cytoplasmatic sequestration of HLH/

bHLH proteins, reduced proliferation, increased cytotoxicity and reduced

clonogenic survival in vitro. In vivo experiments showed a longer latency

for symptom onset. CAGE and RNA-seq analysis pointed to alterations in

several cancer-related pathways.

Conclusions: dnE47-mediated inhibition of HLH/bHLH networks in-

duced actionable molecular alterations in glioma that could be exploited

to develop novel therapies.

Disclosure Statement: MK received funds from Elfriede Kröner Stiung, GT

served on Advisory Boards of BMS, MSD and AbbVie; received research and/or

travel grants from Roche Diagnostics, Novocure and Medac; received speaker’s

fees from Medac, Novocure

584

Pretreatment with the mTOR Inhibitor Everolimus Enhances

Glioblastoma Sensitivity to Temozolomide in Vitro

Aaron Lawson McLean; Diana Freitag; Rolf Kal; Jan Walter

Klinik für Neurochirurgie, Universitätsklinikum Jena, Jena, Deutschland

Purpose: Glioblastoma (GBM) is the most invasive and devastating pri-

mary brain tumor with a median overall survival time of 18 months de-

spite aggressive multimodal therapy. New therapeutic strategies, poten-

tially involving multistage chemotherapy regimens, are needed to enhance

survival. is applies not only in the setting of progressive disease but also

in frontline protocols.

Methods: Four distinct primary GBM cell cultures were treated with the

mTOR inhibitor everolimus and/or the tyrosine kinase inhibitor axitinib.

Untreated cell cultures and cultures treated with the corresponding vehicle

(ethanol and/or DMSO) acted as controls. Treatment was applied to each

culture once and the IC10, IC25 and IC50 concentrations previously

determined by MTT assay were used. Surviving cells were cultured for

three passages and then tested for chemosensitivity to lomustine and

temozolomide.

Results: Cells resistant to the initial treatment could be cultivated in all

study groups. However, cells treated with the combination of everolimus

and axitinib, and with axitinib alone (IC25 and IC50), showed the stron-

gest treatment eects. Cells in these groups no longer adhered to the sub-

strate of culture vessels aer two passages. Cells that could be cultured

showed no signicant dierence in chemosensitivity to lomustine aer

pretreatment. However, cells treated with everolimus were signicantly

more sensitive to temozolomide. Vehicle pretreatment was also associated

with a trend towards increased temozolomide sensitivity.

Conclusions: Everolimus pretreatment strongly enhances GBM cell che-

mosensitivity to temozolomide. is nding may have relevance for GBM

treatment strategies and should now be explored in vivo.

Disclosure Statement: e authors report no conicts of interest.

655

Analysis of Possible Inuence of Cortex Temperature

on Patient Cognition during Awake-Surgery

Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;

Hans-Jakob Steiger; Daniel Hänggi; Michael Sabel

Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland

Purpose: During skull trepanning, it is possible to observe an intraop-

erative heat loss at the brain surface due to convection as well as thermal

radiation. is eect is intensied involuntarily, when rinsing uid adapts

to room temperature during surgery, or intentionally, when cerebral sei-

zures are stopped by active ice-water rinsing. However, the patient’s active

cognitive cooperation is essential, especially during awake phase. e aim

of this pilot study is to investigate the inuence of cortex temperature on

cognition during awake-surgery.

Methods: During an awake-surgery, the complete course of the cortex’s

temperature was analysed continuously by an imaging camera. is was

performed with 8 patients at a total of 52 measuring points. e body’s

core and the cortical temperature changes were determined over time –

split into phases where no water, warm ush (36°C) or ice water was used.

As a surrogate for the cognitive performance of patients, a reaction time

test was performed intraoperatively on the patient.

Results: During the rst measurement the cortex’s temperature was

37.1°C (36.2-37.5°C). e cortex’s surface temperature approached room

temperature (median: 26.2°C) without proper regular irrigation (mean -

1.1°C in the rst 10 min, mean - 2.4°C in the rst 15 min).

Average reaction time was 742 milliseconds. At the same time, average

reaction time at a cortex temperature < 35°C was 1421 milliseconds, at a

cortex temperature 35°C 572 milliseconds (p < 0.05). At a cortex tempera-

ture < 35°C, reaction time improved again aer rinsing with warm liquid.

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Conclusions: Our pilot study suggests a continuous drop in the cerebral

cortex’s temperature during (awake) phase of surgery. Furthermore; the

average reaction time correlated with the temperature of the cortex sig-

nicantly. e brain’s temperature may have signicant impact on the

cognitive performance of patients during the awake phase. is possible

connection should be investigated in further studies.

658

Evaluation of MRI-Artefacts After Removal of Cerebral

Applied Iron Oxide Particles in a Sheep Brain Model

Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;

Jan Frederick Cornelius; Hans-Jakob Steiger; Daniel Hänggi;

Michael Sabel

Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland

Purpose: A possible adjuvant therapy method for patients with recurrent

glioblastoma multiforme is the intra-tumoral application of magnetic iron

oxide particles and the excitation of these particles by an alternating mag-

netic eld. By using this method cancer-killing mechanism should be in-

duced. An obvious problem is the fact that further MRI follow-up checks

are no longer possible aer insertion of metal into the skull because of

artefacts. Our study’s aim is to evaluate the possibility of post-interven-

tional removal of iron oxide particles ex-vivo that would allow subsequent

morphological imaging.

Methods: A precisely dened amount of iron oxide particles (applied via

carrier material) was injected into ex-vivo sheep brains. Subsequently,

brains were heated to 45°C in water for 30 minutes, approaching heat-gen-

erating activation mechanism and demonstrated on the MRI. Subse-

quently, the particles (1) were removed by rinsing (0.9% NaCl) and (2) by

means of ultrasonic aspirator. In a third group, only the carrier material

was removed. e completeness of the iron oxide particles’ removal was

quantied on the MRI.

Results: e experiments were performed on a total of three sheep brains.

When particles were enclosed, pronounced artefacts were found on the

MRI. Aer removal via extensive irrigation or usage of an ultrasound

aspirator, the MRI could no longer detect any iron oxide induced arte-

facts. By selective removal of the carrier material, pronounced artefacts

remained aerwards.

Conclusions: A complete removal of iron oxide particles ex-vivo allowing

an artefact-free MRI imaging seems to be possible. Further studies must

show whether this is possible in-vivo.

660

Comparison of the Cerebral Thermal Ambient Temperature

During the Use of Conventional Coagulation Forceps and

Coagulation Forceps with Active Heat Conduction

Johannes Knipps; Marcel Alexander Kamp; Marion Rapp;

Jan Frederick Cornelius; Hans-Jakob Steiger; Daniel Hänggi;

Michael Sabel

Klinik für Neurochirurgie, Uniklinik Düsseldorf, Düsseldorf, Deutschland

Purpose: Bipolar coagulation forceps are currently used as standard

during (neuro-) surgical operations. Principle of the forceps is based on

heat production that eects a thermally induced tissue coagulation. At the

same time, a heat-related environmental reaction occurs, which can also

be accompanied by damage to the surrounding physiological tissue. e

aim of our study is to compare ambient temperatures aer coagulation

with conventional coagulation forceps and coagulation forceps with active

heat conduction.

Methods: We used an ex-vivo sheep brain model developed at our labo-

ratory: for this purpose, an area of sheep brains encompassing 4mm2 was

coagulated ex-vivo (with a surface temperature of 28°C), within a xed

time of 5 seconds, using 1.) conventional coagulation forceps (Bipolar)

and 2.) coagulation forceps with active heat conduction (Iso). roughout

the process, the temperature of the coagulation area and surrounding tis-

sue was documented by means of a thermal imaging camera during and

aer coagulation, being subsequently evaluated electronically.

Results: e experiments were carried out on a total of four sheep brains.

We were able to show that during the use of conventional coagulation

forceps temperatures above the previously measured surface temperature

could still be measured several centimetres away from the coagulation

area (mean Tmax: 86.75°C, ambient reaction 1cm: 42.8°C). Compared to

that result, the rise of the ambient temperature was signicantly lower

when coagulation forceps with active heat conduction were used (mean

Tmax: 46.9°C), ambient reaction 1cm: mean 34.0°C.

Conclusions: Our thermography measurements have proven that even

several centimetres away from the actual coagulation area, increased and

thus potentially harmful temperatures can be found and shown on the tis-

sue. Since heat has a toxic eect on brain tissue; the application and inten-

sity of coagulation forceps should be used carefully. More recent surgical

instruments with active heat conduction seem to be helpful in reducing

collateral damage due to heat exposure.

Developmental Therapeutics: Cytotoxic Chemotherapy

Poster

848

High Throughput Drug Screening on Pleural Eusion for

Optimizing Cytotoxic Treatment in Metastatic Breast Cancer

Peter Ugocsai 1; Christian Werno 2; Valeria Gerthofer 1; Kathrin Weidele 2;

Natasa Stojanovic 2; Ste Treitschke 2; Kamran Honarnejad 2;

Christoph Andreas Klein 3; Olaf Ortmann 1; Stephan Seitz 1

1Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

2Fraunhofer-Institute for Toxicology and Experimental Medicine, Regensburg,

Deutschland

3Department of Experimental Medicine and Therapy Research,University

Medical Center Regensburg, Regensburg, Deutschland

Purpose: Finding the optimal beyond 2nd line therapeutic strategy in met-

astatic breast cancer (mBC) is challenging. Ex vivo drug tests on patient´s

cancer cells may help to identify eective substances, however despite of a

good correlation between ex vivo test results and in vivo therapy response,

the required time for drug testing (cell isolation, expansion and drug re-

sponse test) is far beyond the possibilities of clinical utilization, in combi-

nation with a low number of candidate drugs tested. We introduce here a

novel approach for ex vivo high throughput drug screening on malignant

pleural eusion to identify substances for an eective beyond 2nd line cy-

totoxic treatment.

Methods: For an optimal analysis of in vitro drug response a suspension of

single cells with high number of tumor cells is required. Malignant pleu-

ral eusion of 5 mBC patients was analyzed for eligibility. Drug response

assays using a drug library of 133 agents were tested at 5 concentrations in

duplicates using an in vitro viability assay for reproducibility and correla-

tion to the retrospective clinical course of the patients.

Results: Malignant cell count in the analyzed pleural eusions (>200ml)

was sucient in all cases to generate a standardized single cell suspension

for drug testing. Drug response assays were successfully carried out in all

5 cases, providing results within 96 hours aer pleural puncture. e in

vitro reproducibility was 100% in repeated tests. We also detected a 100%

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2018

correlation between the in vitro test results of non-responding drugs and

retrospective clinical progress under the corresponding cytotoxic agent.

Conclusions: High throughput drug response screens can be successfully

carried out on pleural eusion within 4 days. e high number of cytotox-

ic agents and the rapid testing allow the identication of drug candidates

for beyond 2nd line treatment in rapidly progressing mBC. Further investi-

gations are required for the assessment of the prospective prognostic val-

ue. e need for pleural eusion is also a current limitation.

Disclosure Statement: no conict of interest

Developmental Therapeutics: Immunotherapy/Cellular Therapy

Best-of-Abstracts-Vorträge

467

CAR-T Cells Directed Against B Cell Surface Antigens for the

Targeting of B Cell Non-Hodgkin’s Lymphoma

Mario Bunse 1; Janina Pfeilschifter 1; Julia Bluhm 1; Wolfgang Uckert 1;

Jörg Westermann 2; Armin Rehm 1; Maria Zschummel 1; Uta Höpken 1

1Berlin, Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland

2Berlin, Charite-University Medicine, Berlin, Deutschland

Purpose: Chimeric antigen receptor (CAR)-T cell therapy is a new type

of cellular immunotherapy that is based on the adoptive transfer of au-

tologous T cells genetically modied with an engineered immunoglob-

ulin-derived receptor that recognizes tumor-associated antigens. CAR-T

cell therapies targeted at the CD19 antigen on leukemia and lymphoma

B cells showed substantial clinical ecacy, currently, more than 40 CD19

CAR-T cell studies are registered at the FDA for the treatment of B-NHL

and B-ALL. However, anti-CD19 CAR-T cell therapy can become inef-

fective due to CD19 antigen loss. is signies the development of im-

munotherapies for additional tumor-associated targets, either for salvage

therapy, or as an alternative to anti-CD19 CARs.

Methods and Results: Here, we identied a B cell homing receptor as an

alternative target for CAR-T cell immunotherapy of mature B cell lym-

phomas by demonstrating strong surface expression of CXCR5 on B-NHL

cell lines but also on primary tumor samples. Based on an anti-human

CXCR5 antibody, we designed a humanized scFv that was incorporat-

ed into a second-generation CAR backbone to generate the anti-human

CXCR5 CAR. e CXCR5 CAR endows T cells with high avidity, neces-

sary for anti-tumor ecacy on lymphoma cell lines, and on primary pa-

tient-derived B-NHL cells. Also, the CXCR5 CAR confers T cell-reactivity

against benign mature B cells, and concomitantly reacts towards lympho-

ma-supportive T cells. No unwanted T cell-reactivity against myeloid

cells and various non-hematopoetic cells from human tissues were ob-

served. A syngeneic mouse model of anti-CXCR5 CAR-T cell therapy was

used to further prove absence of unexpected on-target/o-tumor eects

in-vivo. Finally, CXCR5 CAR-T cells exhibit a robust in-vivo antitumor

activity in a mouse xenogra model ofhuman B-NHL.

Conclusions: We propose CXCR5-targeted CAR-T cells as an attractive

alternative treatment strategy for B-NHL through combined elimination

of lymphoma and tumor-supporting T cells.

Disclosure Statement: All authors declare that they have no competing interests.

Vorträge

819

Feasibility of Autologous Lymphocyte Apheresis in Heavily-

Pretreated Patients Intended to Undergo Therapy with

Chimeric Antigen Receptor (CAR)-T Cells

Vladan Vucinic 1, 1; Saskia Hell 1; David Beverungen 1; Enrica Bach 1;

Sabine Leiblein 1; Michael Cross 1; Madlen Jentzsch 1; Yvonne Remane 2;

Andrea Hille 1; Sandra Otto 1; Elena Ruschpler 1; Uwe Platzbecker 1

1Universitätsklinikum Leipzig AöR, Medizinische Klinik I, Leipzig, Deutschland

2Universitätsklinikum Leipzig AöR, Apotheke, Leipzig, Deutschland

Purpose: One of the essential steps in manufacturing CAR-T cells is the

apheresis of autologous CD3+ lymphocytes. However, due to previous cy-

totoxic therapy, lymphopenia or disease status it is not always possible to

perform a sucient collection. Here we evaluated the feasibility of collect-

ing adequate apheresis products.

Results: Between February and August 2019, we performed 15 collec-

tions in 12 patients with relapse/refractory diuse large B cell Lymphoma

(DLBCL) for subsequent scheduled CAR-T cell therapy (Kymriah®). e

median age was 56 (30-71) and 3 patients were female. In median the pa-

tients had received 4 prior treatments (3-6). Prior to apheresis the mean

white blood cell count (WBC) was 5500/µl (2000-14000) while absolute

lymphocyte count (ALC) was 640/µl (240-1390). All patients underwent a

large volume apheresis (4 x total blood volume) on a Spectra Optia device.

In 14/15 patients the target numbers of CD3+ cells were collected. e to-

tal count of collected CD3 cells was mean 6,8x109 (2,2-16,2), the yield was

mean 0,8x108/kg body weight (0,06-1,91). In 1 patient the collection was

performed in severe lymphopenia (240/µl) thus not reaching the minimal

yield of CD3+ cells. A consecutive collection aer one month was success-

ful. Vitality aer thawing reached >50% in all collections, median 82,1%

(68,8-94,2). Nevertheless, proliferation of lymphocytes aer transduction

in 3 collections (2 patients) was insucient thus terminating the produc-

tion of CAR T product.

Conclusions: In most patients intended to undergo real-life CAR T-cell

therapy adequate numbers of CD3 cells can be collected.

Reference:

1. Allen ES, Stroncek DF, Ren J, Eder AF, West KA, Fry TJ, Lee DW, Mackall CL,

Conry-Cantilena C. Autologous lymphapheresis for the production of chimeric

antigen receptor Tcells. Transfusion. 2017 May;57(5):1133-1141. doi: 10.1111/

trf.14003. Epub 2017 Feb 24.

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Poster

255

Modulation of Antibody-Dependent Phagocytosis by

Macrophages under Metabolic Regulation in the Tumor

Microenvironment

Anna Beielstein 1, 2; Nadine Nickel 2; Elena Izquiero Alvalrez 2;

Daniela Vorholt 2; Samruddhi Schawan 2; Indra Möllenkötte 2;

Michael Hallek 1, 2; Christian P. Pallasch 1, 2

1Department I for Internal Medicine, University Hospital of Cologne, Cologne,

Deutschland

2CECAD Center of Excellence, CECAD Research Center, Cologne, Deutschland

Purpose: erapy response in B-cell lymphoma by chemoimmunother-

apy largely depends on the tumor microenvironment and the functional

status of macrophages as important eector cells. Within the tumor mi-

croenvironment a limited supply of nutrients leads to metabolic alter-

ations in malignant cells as well as an altered immune system.

Methods: As macrophage function is sensitive to metabolic alterations,

we addressed macrophage lymphoma cell co-cultures to assess the im-

pact of metabolic pathway inhibition (using several pathway inhibitors)

on antibody-dependent cellular phagocytosis (ADCP). We particularly

aim to improve macrophage eector cell function in the context of im-

munotherapy.

Results: Inhibition of AMP kinase, glycolysis or the ATP-production

had no positive eect on the phagocytosis rate. However, inhibiting the

pentose phosphate pathway (PPP) by Oxythiamine, p-Hydroxyphenylpy-

ruvate, Physcion and 6-Aminonicotinamide leads to an increased target

cell phagocytosis and Fc-receptor expression in independent eector cell

types (J774A1 and THP1). In this line metabolites of the PPP could be

shown to similarly aect ADCP by adding educts and products of the

PPP signicantly altering the macrophage-mediated target cell depletion.

ese changes could also be seen in PPP-enzyme knockdown (transketo-

lase and 6-PGD) in macrophages and by inhibiting the PPP in primary

murine and human macrophages.

We subsequently performed a proteomic analysis of PPP inhibition in

macrophages identifying metabolism and immune regulation related

eects. Specically under PPP-inhibition, Seahorse analysis showed in-

creased oxygen consumption and glycolysis of macrophages. Further-

more, the eector cells showed enlarged morphology and developed an

activated phenotype.

Conclusions: We hypothesize the PPP as a regulator of macrophage activ-

ity determining therapy outcome and aim to identify specic modulators

of macrophage polarization and function in tumor immunotherapy.

Disclosure Statement: No conict of Interest. A.B. was supported by Köln fortune

scholarship

482

A Phase 3 Randomized, Open-Label, Multicenter Study

Comparing Isatuximab, Pomalidomide, and Low-Dose

Dexamethasone Versus Pomalidomide and Low-Dose

Dexamethasone in Patients with Relapsed / Multiple Myeloma

Refractory (RRMM)

Dietger Niederwieser 1; Paul Richardson 2; Michel Attal 3; Vincent

Rajkumar 4; Jesus San-Miguel 5; Meral Beksac 6; Ivan Spicka 7; Xavier Leleu 8;

Fredrik Schjesvold 9, 10; Philippe Moreau 11; Meletios Dimopoulos 12;

Jerey Shang-Yi Huan 13; Jiri Minarik 14; Michele Cavo 15; Sandrine Macé 16;

H. Miles Prince 17; Kathryn P. Corzo 18; Frank Campana 18;

Solenn Le-Guennec 16; Franck Dubin 16; Kenneth C. Anderson on Behalf

of the Icaria-MM Study Group 2

1University of Leipzig, Leipzig, Deutschland

2Dana-Farber Cancer Institute, Harvard Medical School, Boston, United States

3Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, Frankreich

4Mayo Clinic, Rochester, United States

5Clínica Universidad de Navarra, Navarra, Spanien

6Ankara University, Ankara, Turkey

7Charles University in Prague, Prague, Tschechien

8Hopital Claude Huriez, CHRU Lille, Lille, Frankreich

9Oslo Myeloma Center, Oslo University Hospital, Oslo, Norwegen

10KG Jebsen Center for B cell malignancies, University of Oslo, Oslo, Norwegen

11CHU Nantes, Nantes, Frankreich

12National and Kapodistrian University of Athens, Athens, Griechenland

13National Taiwan University Hospital, Taiwan

14University Hospital Olomouc, Olomouc, Tschechien

15Univeristy of Bologna, Bologna, Italien

16Sano R & D, Vitry-Alfortville, Frankreich

17Epworth Healthcare and Peter MacCallum Cancer Centre, University of

Melbourne, Victoria, Australien

18Sano-Genzyme Oncology, Cambridge, United States

Purpose: To demonstrate the benet of isatuximab (Isa), a novel an-

ti-CD38 monoclonal antibody, combined with pomalidomide (P)/

dexamethasone (d) versus (vs) Pd, on progression free survival (PFS) in

RRMM patients (pts).

Methods: Pts who received ≥2 prior lines, including lenalidomide (len)

and a proteasome inhibitor (PI), refractory to last therapy were enrolled

in this phase 3 trial (NCT02990338). IsaPd arm received Isa 10 mg/kg IV

weekly for rst 4 weeks (wks), then every 2 wks. Both arms received ap-

proved schedules of P and d (4mg PO days 1-21; 40mg [20mg if >75 yrs]

PO or IV weekly) every 28 days until progression or unacceptable toxicity.

Results: 307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT).

Patient characteristics were well balanced across treatment arms. Medi-

an age: 67 (36-86) yrs; median prior lines of therapy: 3 (2-11); estimated

GFR: <60ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and

19.5% pts had high-risk cytogenetics. At median follow-up (11.6 months

[mos]), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95%

CI 0.44-0.81), P=0.001. PFS benet was consistent across all major sub-

groups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P<0.0001. VGPR rate

or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10-5)

was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS)

was immature (99 events) but a trend to OS improvement in IsaPd vs Pd

was observed (HR 0.687; 95% CI 0.461-1.023). Median treatment dura-

tion was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration

was 3.3h at 1st inf. and 2.8h at subsequent inf. Grade ≥3 AEs were observed

in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued

due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions

were reported in 38.2% (2.6% grade 3-4) IsaPd. Grade ≥3 infections were

seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile

11.8%) IsaPd and 70.1% (febrile 2.0%) Pd.

Conclusions: IsaPd signicantly improved PFS and ORR vs Pd, with a

manageable safety prole. IsaPd is an important new treatment option for

the management of RRMM.

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is abstract was previously presented atAmerican Society of Clinical

Oncology (ASCO)2019Annual Meeting, May 31–June 4, Chicago IL,

and encored at the European Hematology Association (EHA) June 13–16,

2019, Amsterdam, Netherlands

Disclosure Statement

DIETGER W. NIEDERWIESER: No conicts of interest.

PAUL G. RICHARDSON: Consulting or Advisory Role – Karyopharm; Onco-

peptides; Celgene; Janssen; Takeda; Sano; Research Funding - Oncopeptides,

Celgene; Takeda, BMS.

MICHEL ATTAL: Research Funding – Sano.

S. VINCENT RAJKUMAR: No conicts of interest.

JESUS SAN-MIGUEL: Consulting or Advisory Role - Amgen; Bristol-Myers

Squibb; Celgene; Janssen; MSD; Novartis; Roche; Sano; Takeda.

MERAL BEKSAC: Consulting or Advisory Role - Amgen (Inst); Celgene (Inst);

Janssen-Cilag (Inst); Takeda (Inst); Speakers’ Bureau - Amgen; Bristol-Myers

Squibb; Celgene; Janssen-Cilag.

IVAN SPICKA: Consulting or Advisory Role - Amgen; Bristol-Myers-Squibb;

Celgene; Janssen-Cilag; Novartis; Takeda; Speakers’ Bureau - Amgen; Bristol-

Myers-Squibb; Celgene; Janssen-Cilag; Novartis; Takeda.

XAVIER LELEU: Honoraria - Abbvie; Amgen; Bristol-Myers Squibb; Carsgen

erapeutics Ltd; Celgene; Janssen-Cilag; Karyopharm erapeutics; Merck;

Mundipharma; Novartis; Oncopeptides; Pierre Fabre; Roche; Sano; Takeda;

Consulting or Advisory Role - Abbvie; Amgen; Bristol-Myers Squibb; Carsgen

erapeutics Ltd; Celgene; Gilead Sciences; Janssen-Cilag; Karyopharm era-

peutics; Merck; Mundipharma; Novartis; Oncopeptides; Roche; Takeda; Travel,

Accommodations, Expenses – Takeda.

FREDRIK SCHJESVOLD: Honoraria - Abbvie; Amgen; Celgene; Janssen China

R&D; Novartis; Takeda; Consulting or Advisory Role - Adaptive Biotechnologies;

Amgen; Bayer; Bristol-Myers-Squibb; Celgene; Janssen China R&D; Oncopeptides;

Takeda; Research Funding - Amgen; Janssen China R&D.

PHILIPPE MOREAU: Honoraria - Amgen; Celgene; Janssen-Cilag; Novartis;

Takeda; Consulting or Advisory Role - Amgen; Celgene; Janssen; Novartis; Takeda.

MELETIOS A DIMOPOULOS: Honoraria -Celgene, Takeda, BMS, Janssen and

Amgen; Consulting or Advisory Role - Amgen; Bristol-Myers Squibb; Celgene;

Janssen-Cilag; Takeda.

JEFFREY SHANG-YI HUANG: Research Funding – Sano.

JIRI MINARIK: Consultancy and Honoraria - Amgen, BMS, Celgene, Janssen,

Takeda Clinical trials investigator - Amgen, Janssen, Karyopharm, Oncopeptides,

Sano.

MICHELE CAVO: Honoraria - Abbvie; Adaptive Biotechnologies; Amgen; Bristol-

Myers-Squibb; Celgene; GlaxoSmithKline; Janssen China R&D; Takeda; Consult-

ing or Advisory Role - Abbvie; Adaptive Biotechnologies; Amgen; Bristol-Myers-

Squibb; Celgene; GlaxoSmithKline; Janssen China R&D; Takeda; Speakers’

Bureau - Celgene; Janssen China R&D.

H. MILES PRINCE: Honoraria - Amgen; Celgene; Janssen China R&D; Novartis;

Takeda; Consulting or Advisory Role – Amgen; Celgene; Janssen China R&D;

Novartis; Takeda; Research Funding – Sano; Takeda.

KENNETH C. ANDERSON: Stock and Other Ownership Interests - C4 era-

peutics; OncoPep; Consulting or Advisory Role – Bristol-Myers Squibb; Celgene;

Gilead Sciences; Janssen Oncology; Millennium; Sano; Patents, Royalties, Other

Intellectual

Property - C4 erapeutics; Oncopep.

SANDRINE MACÉ, KATHRYN P. CORZO, FRANK CAMPANA, SOLENN

LEGUENNEC, FRANCK DUBIN are employees of Sano.

776

CAR T-Cell Therapy in the Real World Setting: Predictive

Factors for Successful Bridging between Apheresis and Car

T-Cell Infusion

Georg-Nikolaus Franke; Eberhard Schleyer; Konstantin Weibl;

Hansjakob Fries; Sophia Michel; Rosmarie Pointner; Dominic Brauer;

Andrea Hille; Sandra Otto; Uwe Platzbecker; Vladan Vucinic

Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Leipzig,

Deutschland

Purpose: CAR T-cells directed against CD19 are a newly approved cel-

lular therapy for treating patients (pts) with relapsed or refractory (r/r)

pediatric and adolescent acute lymphoblastic leukemia or diuse large

B-cell lymphomas (DLBCL). Bridging pts from lymphapheresis (LA) to

infusion of CAR T-cells remains challenging given the aggressive nature

of the disease. Little is known on predictive factors aecting this period of

manufacturing in the real-world population.

Methods: We evaluated the potential of clinical variables aecting success

of CAR-T reinfusion in pts receiving CD19 CAR tisagenlecleucel at our

CAR T-cell center.

Results: Nine pts were allocated to receive CARs and underwent apheresis

between May to August 2019 for r/r DLBCL. 3 pts died prior to infusion. 6

pts received CARs aer a median time of 49 days aer LA. Pts not receiv-

ing the CAR infusion presented with higher lactate dehydrogenase (LDH)

and C-reactive protein (CrP), worse ECOG performance status (PS) at the

time of LA, had obtained more lines of therapy and were more likely treat-

ed in an external hospital than patients receiving the CARs. We developed

a scoring system in order to predict outcome based on these factors. CrP

and LDH above the median were assigned 2 points (p.) each, the ECOG

PS at the time of LA were added, and each line of therapy aer 1st salvage

was assigned 1 p. and referral from an external hospital therapy 1 p. Pts

achieving a score of 5 or higher were at high risk to die prior to infusion:

3 out of 4 patients did not undergo CAR T-cell infusion. In contrast, pts

receiving the CARs had a median score of 2.5 (range 1-6).

Conclusions: Bridging eligible patients to from LA to CD19 CARs infu-

sion remains a challenge. e proposed score may help to identify pts at

high risk for complications rendering the CAR T-cell infusion impossible.

We aim to evaluate the score in a larger group of pts.

Disclosure: the authors have nothing to disclose

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Developmental Therapeutics: Molecular Therapeutics

Best-of-Abstracts-Vorträge

188

Identication of Novel Notch1-Regulated Therapeutic Targets

in Multiple Myeloma through Functional shRNA-Based

Screening

Daniela Simone Maichl 1; Fani Ziouti 1; Julius Arthur Kirner 1;

Stefanie Schmidt 1, 2; Carsten Patrick Ade 2; Sascha Dietrich 3;

Tobias Heckel 3; Franziska Jundt 1

1Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg,

Deutschland

2Universität Würzburg, Lehrstuhl für Biochemie und Molekularbiologie,

Würzburg, Deutschland

3Universität Würzburg, Core Unit Systemmedizin, Würzburg, Deutschland

Purpose: Aberrantly activated Notch signaling promotes multiple myelo-

ma (MM) onset, progression and drug resistance. As inhibition of Notch

activation using γ-secretase inhibitors is impeded by serious side eects,

there is still the need for the development of novel specic therapeutic

strategies. e present study aims to address this challenge and identify

novel druggable downstream eectors of the Notch1 pathway by employ-

ing shRNA-based functional high throughput (HT) screening.

Methods: First, we performed transcriptome proling in MM.1S cells to

identify Notch1-regulated genes. Of 842 genes dierentially expressed

aer Notch1 inhibition, we selected 40 consistently and strongly down-

regulated genes for a tailored shRNA library. Negative selection screens

employing the library were carried out in U266 cells modied to ex-

clusively express the Notch1 intracellular domain (NIC) or the Notch1

variant N∆E. Aer cultivation for 12 days under the selective pressure of

melphalan, bortezomib or lenalidomide, treated cells and controls were

harvested. Subsequently, shRNA sequences were recovered from genomic

DNA using PCR and changes in their representation were analyzed bioin-

formatically aer HT sequencing.

Results: Analysis of dierential shRNA representation of the rst screen

with lenalidomide was recently completed. Based on standard deviation

scores (z-scores; cut-o>-2), we ranked the shRNAs and further evaluat-

ed the druggability of the corresponding target gene/protein. Finally, we

chose 4 candidate genes - 3 transcription factors and one enzyme - drug-

gable with already available small molecule inhibitors. In vitro validation

of candidate genes will comprise treatment of MM cell lines with a chem-

ical inhibitor or specic shRNAs in combination with lenalidomide. Re-

sults of the bioinformatic analysis of the screens and in vitro validation of

screen hits will be presented in detail at the DKK 2020.

Conclusions: Study results hold the potential for the development of nov-

el MM treatment strategies.

Disclosure Statement: No conicts of interest.

Poster

563

NTRK Fusion-Tumors in Adult Cancer Patients – Single Center

Report on Screening and Treatment

Florian Länger 1; Hendrik Eggers 2; Ralf Gutzmer 3; Imke Satzger 3;

Christian von Falck 4; Arnold Ganser 2; Hans H. Kreipe 1; Viktor Grünwald 5;

Philipp Ivanyi 2

1Medizinische Hochschule Hannover, Institut für Pathologie, MHH, Hannover

2Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,

Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,

Deutschland

3Klinik für Dermatologie, Allergologie und Venerologie der Medizinischen

Hochschule Hannover, Hannover, Deutschland

4Medizinische Hochschule Hannover (MHH) Institut für Diagnostische

Radiologie, Hannover, Deutschland

5Westdeutsches Tumorzentrum Essen, Essen, Deutschland

Purpose: Neurotropic tropomyosin-related kinases (NTRK) are involved

in neuronal processes. Oncogenic NTRK gene-fusions are rare but prom-

ising targets for tyrosine kinase inhibitors (TKI). We report on feasibility

of screening and treatment of NTRK-fusions during oncology routine.

Methods: Patients (pts) with malignant diseases of mainly Head and

Neck (HNSCC), salivary glands (SGT), thyroid (TC), so tissue (STS),

bone (BS), kidney (RCC), melanocytes (MM) were screened. Primarily,

NTRK-immunhistochemistry (IHC) (EPR17341, Abcam) and FISH anal-

yses were done for ETV6 (Abbott Vysis). Once screening was positive,

RNA based NGS analyses was performed (RNA-Oncomine-Focus-Assay,

ermo Fisher). NTRK positive pts were treated with TKI larotrectnib, if

applicable.

Results: From 12/18-8/19 108 pts were screened. Pts were at median 53.7

(range (r), 15.8 - 89.9) years old and received 1.5 lines (r, 0 – 8) of che-

motherapy at time of screening. 3 (2.7 %) pts were NTRK-IHC positive,

and NGS conrmed NTRK-fusion in 2 pts (1.85 %) (TPM3-NTRK1 and

ETV6(5)-NTRK3(15)). One NTRK positive TC-pts received larotrectinib,

resulting in an ongoing good response.

Conclusions: NTRK testing is feasible during oncological routine upon

interdisciplinary established screening strategy. In 1.85 % of screened pts

NTRK-fusion-tumour was proven. is incidence is higher than expect-

ed, which might result from our selected screening cohort. However, in

one pts without therapeutic options NTRK screening enabled TKI admin-

istration resulting in highly eective treatment. Testing algorithm needs

to be discussed interdisciplinarily in particular when several NTRK inhib-

itors will be available, to ensure NTRK-inhibition as a therapeutic option

for patients with NTRK-fusion-tumours.

Dislosure Statement: FL, VG, PI received lecture honoraria and advisory fees

from Bayer and Roche.

723

Tumor-Biological Eects of Acetylsalicylic Acid and Ascorbic

Acid Regarding the HIF1 Level

Matthias Kappler 1; Ulrike Pabst 1; Dirk Vordermark 2; Alexander W. Eckert 1

1Department of Oral and Maxillofacial Plastic Surgery , Martin Luther University

Halle-Wittenberg, Halle (Saale), Deutschland

2Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Halle

(Saale), Deutschland

Purpose: Treatment with acetylsalicylic acid (ASA) positively aects the

prognosis of various tumor entities (Rothwell et al., 2012). A similar benet

for tumor patients was found for a treatment with ascorbic acid (vit c)

(Kuiper et al., 2014). It appears that the activity of the transcription factor

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HIF1 could be reduced by these treatments. HIF1 is a regulator of genes

involved in hypoxic metabolism/glycolysis but also inuences normoxic

metabolism/glutaminolysis. In addition, HIF1-level is associated with a

poorer outcome of tumor patients and drives the process of metastasis

(Rankin et al., 2016).

Methods: We examined in tumor cell lines the eect of ASA and vit c on

the expression of HIF1 and/or its tumor biological/metabolic inuence.

Results: We found that ASA and vit c reduced the expression level of nor-

moxic HIF1 and ASA even reduced the hypoxic HIF1 level. is is caused

by the ability of ASA to alter the acetylation status and thus the stability

of proteins (Tatham et al., 2017) like HIF1. Vit c appears to impair the

functionality of mitochondria and aected the normoxic HIF1 stability

and the amino acid metabolism, also independently of HIF1.

Conclusions: Both substances are able to inhibit the activity of HIF1. is

inhibition could partly explain the tumor-therapeutic eect of ASA and

vit c. A possible support of tumor therapies with ASA & vit c appears to

be a useful adjunction for the treatment of both normoxic and hypoxic

tumors.

References:

1. Tatham et al., MCP 2017, 16, 310–326.

2. Rothwell et al., e Lancet 2012, 379, 1602–1612.

3. Kuiper et al., Frontiers in oncology 2014, 4, 10.

4. Rankin et al., Science 2016, 352, 175–180.

Endocrine Tumor (e. g. Thyroid Cancer, Adrenal Tumor, Neuroendocrine Tumor)

Poster

589

Characterization of Epigenetic Modulation in Pancreatic

Neuroendocrine Neoplasms

Rosa Lynn Schmitz; Julia Weißbach; Jan Kleilein; Patrick Michl;

Sebastian Krug

University Hospital Halle (Saale), Clinic for Internal Medicine I, Halle (Saale),

Deutschland

Purpose: Pancreatic neuroendocrine tumors (pNETs) represent a rare

and heterogeneous tumor entity. Despite surgery, several therapeutic ap-

proaches involving biotherapy, target therapy or chemotherapy are appli-

cable. However, cancer progression and resistance mechanisms are still

challenging. Recent genome wide sequencing analyses in pNETs identi-

ed a large number of mutated genes involved in epigenetic modulation.

Targeting epigenetic regulation in tumor cells in combination with specif-

ically triggered immune cells could be a new therapeutic avenue.

Methods: e human pNET cell lines BON-1 and QGP-1, the murine in-

sulinoma cell lines beta-TC-6 and RIN-T3 and the human monocyte-like

THP-1 cells were treated with Panobinostat (PB) and analyzed for func-

tional eects and aected signaling pathways performing Western blot,

FACS and qPCR analyses. Additionally, the impact of PB on microRNA

and lncRNA expression in BON-1 and QGP-1 cells was investigated by

RNA sequencing.

Results: Beside hyper-acetylation, PB clearly induces an apoptotic phe-

notype as well as cell cycle arrest in neuroendocrine cells from various

species. ereby, the eect of PB tends to be mediated by a cluster of dif-

ferentially regulated microRNA and lncRNA. In THP-1 monocytes PB

induces altered macrophage polarization into a more pronounced M1

phenotype, which additionally enhances its tumor-repressing impact in

co-cultivation studies.

Conclusions: Beside its cytotoxic eect on tumor cells, PB also showed

tumor cell-independent inuence due to alteration of the inammatory

stroma. ese results play an important role on tumor progression.

Disclosure Statement: No conict of interest

703

“Routine Usage of Molecular Targeted Therapies (Everolimus

and Sunitinib) and Temozolomide Based Chemotherapy in

Neuroendocrine Neoplasia and Its Outcome”

Sebastian Maasberg 1; Maria Bacher 2; Anja Rinke 3; Harald Lahner 4;

Detlef Quietzsch 5; Bence Sipos 6; Christian Grohé 7; Patricia Grabowski 8;

Nehara Begum 9; Christian Fottner 10; Ulrich-Frank Pape 1

1Innere Medizin, Gastroenterologie und Diabetologie, Asklepios Klinik St. Georg,

Hamburg, Deutschland

2Innere Medizin - Kardiologie und konservative Intensivmedizin, Vivantes

Humboldt Klinikum , Berlin, Deutschland

3Gastroenterologie, Endokrinologie, Stowechsel und klinische Infektiologie,

Universitätsklinikum Gießen Marburg, Standort Marburg, Marburg,

Deutschland

4Klinik für Endokrinologie und Stowechselerkrankungen, Universitätsklinikum

Essen, Essen, Deutschland

5Fachpraxis für Innere Medizin, Oelsnitz, Deutschland

6Fachärztliche Berufsausübungsgemeinschaft für Pathologie und

Molekularpathologie, Stuttgart, Deutschland

7Klinik für Pneumologie, Evangelische Lungenklinik Berlin, Berlin, Deutschland

8Institut für Immunologie, Universitätsmedizin Charité, Berlin

9Allgemein- und Viszeralchirurgie, Agaplesion Ev. Klinikum Schaumburg,

Obernkirchen , Deutschland

10I. Medizinische Klinik und Poliklinik, Schwerpunkt Endokrinologie und

Stowechselerkrankungen, Universitätsmedizin Mainz, Mainz, Deutschland

Purpose: Orally applied targeted therapies everolimus (EV) and sunitinib

(SUN) as well as a temozolomide (TEM) mono- or combination chemo-

therapy (CTx) with capecitabine (CAP) are of increasing importance in

the treatment of neuroendocrine neoplasia (NEN).

Methods: In a multicentric cohort from the German NET-Registry rou-

tine data of NEN pts. with initial diagnosis since 1988 were analyzed with

regards to the usage and outcome of EV, SUN and TEM-based therapies.

Statistical analysis was performed using SPSS version 20.0.

Results: From a total of 3521 patients (pts.) registered within the

NET-Registry database 219 received EV, 61 received SUN and 94 a TEM-

based CTx during the course of the disease. Subgroup analyses due to suf-

cient follow-up information were possible for 81 pts on EV, 36 on SUN

and 66 on a TEM-based CTx. In pts with EV, SUN or a TEM-based CTx

median age was 54 years, 56 years and 54 years, respectively. Primary tu-

mor localization were pancreatic (66%), bronchopulmonal (10%), intes-

tinal (13%) and other localizations (n=4%) or unknown (n=7%). Initial

therapy consisted of EV, SUN or TEM-based CTx in 9%, 6% or 10%, while

31%, 14% and 26% received them as second line treatment. In later ther-

apeutic lines EV was used in 60%, SUN in 77% and a TEM-based CTx in

64% of pts.. Partial remission (PR) as best radiologic response was seen

in 7% of pts. on EV, 23% of pts. on SUN and 24% of pts on a TEM-based

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CTx. Stable disease (SD) was achieved in 64%, 60% and 46% treated with

EV, SUN or a TEM-based CTx. Disease progression was documented in

29%, 17% and 30%, respectively. Median overall survival was 43 months

(m) in the EV group, while 44 m and 43m in the SUN or TEM-based CTx

group. Median time to documented progression (mTTP) was 8, 10 and

8 months in pts. with EV, SUN or a TEM-based CTx and 9 months in a

subgroup of pts. with NET-G2.

Conclusions: Routine treatment of EV; SUN and TEM-based CTx

showed a reasonable response and sucient disease control in advanced

and in part heavily pretreated pts. with neuroendocrine Neoplasia G1/G2

as well as G3.

827

Peritoneal Carcinomatosis Manifestation within the Hernia

Sack of an Inguinal Hernia (Representative Case)

Manuel Bachmann 1; Ste Peglow 1; Manuela Petersen 1; Victor Schoeder 2;

Dörthe Jechorek 2; Frank Meyer 1

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Institute of Pathology, University Hospital at Magdeburg , Magdeburg,

Deutschland

Purpose: Periop. management & surgical treatment of inguinal hernia are

routinely provided.

Method: Scientic case report

Results (case presentation): A 65-years old patient w/ a med. history

signicant for a pararenal gland carcinoma (PRG-Ca) (treated w/ radia-

tion) w/ hepatic metastases & multiple ulcerations of the posterior gastric

wall showed reduced clinical (palpable & painful tumor resistance at the

right lower abdomen) & nutritional status (cachexia). CT scan showed

advanced tumor growth of a PRG-Ca inltrating surrounding organs.

A multivisceral resection was performed comprising adrenalectomy/le

nephrectomy, resection of the pancreatic tail, splenectomy, partial gastric

resection, resection of the le renal vein w/ tumor thrombectomy with-

in the inferior V. cava & patch plasty (xenogra), omentectomy & local

excision of peritoneal tumor lesions. Postoperatively, patient underwent

re-laparotomy to suture a sudden intestinal lesion. During further course,

an irreducible inguinal hernia was diagnosed which was conrmed by ul-

trasound & subsequently repaired by Shouldice’s procedure. e intraop.

suspicion of a peritoneal tumor lesion of the PRG-Ca within the herni-

al sac was conrmed by histopathological investigation. Further postop.

course was uneventful.

Conclusions: An irreducible inguinal hernia w/ manifest nodes of a peri-

toneal carcinomatosis can be assessed a rare but instructive disease in the

broad spectrum of dierential diagnoses of inguinal hernia.

Epidemiology

Poster

122

Socioeconomic Dierences and Lung Cancer Survival in

Germany: Investigation based on Population-Based Clinical

Cancer Registration

Isabelle Finke 1, 2; Gundula Behrens 1; Lars Schwettmann 3; Michael Gerken 4;

Ron Pritzkuleit 5; Bernd Holleczek 6; Hermann Brenner 1, 7, 8; Lina Jansen 1

1Division of Clinical Epidemiology and Aging Research, German Cancer

Research Center (DKFZ), Heidelberg, Deutschland

2Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Deutschland

3Institute of Health Economics and Health Care Management, Helmholtz

Zentrum München - German Research Center for Environmental Health

(GmbH), Neuherberg, Deutschland

4Tumor Center - Institute for Quality Management and Health Services

Research, University of Regensburg, Regensburg, Deutschland

5Institute for Cancer Epidemiology at the University of Lübeck, Cancer Registry

Schleswig-Holstein, Lübeck, Deutschland

6Saarland Cancer Registry, Saarbrücken, Deutschland

7Division of Preventive Oncology, German Cancer Research Center (DKFZ) and

National Center for Tumor Diseases (NCT), Heidelberg, Deutschland

8German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

Purpose: Studies from several countries reported socioeconomic inequal-

ities in lung cancer survival. Hypothesized reasons are dierences in can-

cer care or tumor characteristics. We examined associations of small-area

deprivation and lung cancer survival in Germany and the possible impact

of dierences in patient, tumor or treatment factors.

Methods: Patients registered with a primary tumor of the lung (ICD-10

C34) between 2000-2015 in three German population-based clinical can-

cer registries were included. Area-based socioeconomic deprivation on

municipality level was measured with the categorized German Index of

Multiple Deprivation (GIMD). Our main outcome, survival aer cancer

diagnosis, was analyzed with Cox regression and we repeated the analysis

for subgroups receiving chemotherapy, radiotherapy or surgery. e main

models included age, sex, histologic subtype, grading and stage at diagno-

sis. All analyses were conducted in SAS 9.4.

Results: Overall, 22,905 patients were included of whom 72.9% were

male, 23.8% were over 75 years of age, 49.5% were diagnosed with stage

IV cancer and 82.7% with non-small-cell lung cancer. Kaplan-Meier ve

year overall survival estimates from the least to the most deprived quintile

were 17.2% [95%-Condence Interval (CI): 15.8-18.5], 15.9% [14.8-17.2],

16.7% [15.5-17.9], 15.7% [14.5-16.9], and 14.4% [13.3-15.5], respectively.

Our main Cox model showed lower survival in the most deprived group

compared to the most auent group (Hazard Ratio (HR) 1.06, 95% con-

dence interval (CI) 1.01-1.11). Subgroup analyses showed lower survival

in the most deprived compared to the least deprived quintile for stage I-III

patients [HR: 1.14, 95% CI: 1.06-1.22]. e association persisted when re-

stricting to patients receiving surgery but was attenuated for subgroups

receiving either chemotherapy or radiotherapy.

Conclusions: Our results indicate dierences in lung cancer survival ac-

cording to area-based socioeconomic deprivation on municipality level

in Germany.

Disclosure Statement: e authors declare no conict of interest.

176

Establishing a Valid Approach for Estimating Familial Risk

ofCancer Explained by Common Genetic Variants

Korbinian Weigl 1; Jenny Chang-Claude 2; LI Hsu 3; Michael Homeister 1;

Hermann Brenner 1

1Deutsches Krebsforschungszentrum, Abteilung für Klinische Epidemiologie

und Alternsforschung, Heidelberg, Deutschland

2Deutsches Krebsforschungszentrum, Abteilung für Genetische Epidemiologie,

Heidelberg, Deutschland

3Fred Hutchinson Cancer Research Center, Public Health Science Division,

Seattle, United States

Purpose: To critically examine existing approaches for the estimation

of the excess familial risk of cancer which can be attributed to identi-

ed common genetic risk variants and to propose an alternative, more

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straightforward approach for calculating this proportion using well-estab-

lished epidemiological methodology.

Methods: e underlying equations of the traditional approaches and the

new epidemiological approach were applied for colorectal cancer (CRC)

in a large population-based case-control study in Germany with 4447 cas-

es and 3480 controls, who were recruited from 2003-2016 and for whom

interview, medical and genomic data were available.

Results: Having a family history of CRC (FH) was associated with a 1.77-

fold risk increase in our study population (95% CI 1.52-2.07). Traditional

approaches yielded estimates of the FH-associated risk explained by 97

common genetics variants from 9.6% to 23.1%, depending on various as-

sumptions. Our alternative approach resulted in smaller and more consis-

tent estimates of this proportion, ranging from 5.4% to 14.3%.

Conclusions: Commonly employed methods may lead to strongly diver-

gent and possibly exaggerated estimates of excess familial risk of cancer

explained by associated known common genetic variants. Our results

suggest that familial risk and risk associated with known common genetic

variants might reect two complementary major sources of risk.

Disclosure Statement: e authors have nothing to disclose.

398

Manifestation of Secondary Malignancies of the

Hematopoietic (HP) System in Patients with Tumors

of the Genitourinary (GU) Tract

Bernhard Koch 1; Lutz Uacker 1; Ayoub Abdu 1; Guntram Büsche 2;

Dirk Heimbach 3

1Datteln, St. Vincenz-Krankenhaus, Med. Klinik, Datteln, Deutschland

2Hannover, MHH, Institut für Pathologie, Hannover, Deutschland

3Datteln, St. Vincenz-Krankenhaus, Urologische Klinik, Datteln, Deutschland

Purpose: ere are reports on the increased risk of double malignancies

in patients with GU cancer and lymphomas (1,2). Since immunological

reactions play an important role in the control of tumor growth and since

the immune system is part of the HP system it seems of interest to look

more intensively on double malignancies arising in both systems to even-

tually detect common disturbances behind.

Methods: We searched the data base of our hospital over a period of 15

years for the documentation of double malignancies within the HP sys-

tem and the GU tract. e HP system was represented by acute leukemias

/ myelodysplasias (n=12), lymphomas / CLL (n=33), paraproteinemias /

multiple myelomas (n=12), and myeloproliferative diseases (n=2), and the

GU tract by cancer of the prostate (n=35), the bladder (n=19), and the

kidney (n=5).

Results: We identied 59 patients with double malignancies detected both

in the GU tract and in the HP system either synchronously or metachro-

nously (interval of diagnosis <3 or > 3 months). 66% of patients started

with a primary neoplasm of the GU tract followed by a HP malignancy

metachronously with a median interval time of 6 years. In 19 % of patients

the diagnosis of the HP and GU neoplasm was made synchronously. A

primary malignancy of the HP system was found in 15 % of patients. Rare

patients developed a HP malignancy within the GU tract. A group of 8

patients exhibited 3 malignancies of dierent entities.

Conclusions: Considering the multifactorial background of tumor

growth the occurrence of double malignancies may be associated to cyto-

genetic aberrations, therapeutic interventions, and perhaps immunosup-

pressive conditions due to chronic infections residing outside the tumor

itself in the tumor adjacent microenvironment. e analysis of patients

with multiple malignancies deserves special interest due to an advanced

cancer prone status.

References:

1. van den Broek EC et al., Ann Hematol 2014, PMID 24381068

2. Landgren O et al., Int J Cancer 2006, PMID 17131330

Disclosure Statement: e authors declare no conict of interest.

451

Trends in Cancer Survival in Germany from 1991 to 2016

Stefan Dahm; Benjamin Barnes; Klaus Kraywinkel

Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland

Purpose: Survival rates estimated using data from epidemiological cancer

registries in Germany are dicult to interpret due to regional and tem-

poral variability. One source of uncertainty is the substantial proportion

of cases notied by death certicate only (DCO cases). DCO cases are

usually excluded from survival estimation, but this can lead to biased sur-

vival rates.

Methods: is study is based on data from 4.6 million cancer patients

from 13 federal states diagnosed between 1990 and 2016 and expands

upon previous work [1]. First, relative survival rates were estimated ex-

cluding DCO cases for each registry and year. en, a mixed linear model

controlling for DCO proportions was tted to those estimates. Finally,

based on this model, survival rates and time trends for Germany were

estimated at a DCO proportion of 0%.

Results: e age standardized 1-year relative survival rates for all cancers

combined increased from 47% in 1991 to 73% in 2016, 5-year survival

rates increased from 1995 to 2016 by 25 percentage points to 60%. For

lung cancer, 1-year survival increased by 19 percentage points to 46% and

5-year survival increased from 9% to 18%. For pancreas cancer, 1-year

survival increased from 15% in 1991 to 40% in 2016 and 5-year survival

increased from 2% (1991) to 11% (2016).

Conclusions: e method presented here allows long-term survival

rate estimation based on data from several registries with varying DCO

proportions. Furthermore, the modelling approach uses recent data from

a large number of registries to strengthen estimates could be extended to

the time periods during which only three small registries were in operation.

Reference:

1. DAHM S. BERTZ J. BARNES B. KRAYWINKEL K. (2018) A mixed linear

model controlling for case underascertainment across multiple cancer

registries estimated time trends in survival. Journal of Clinical Epidemiology,

97C, 2018, pp. 123-133

Disclosure Statement: is research did not receive any specic grant from fund-

ing agencies in the public; commercial; or not-for-prot sectors

568

Educational Inequalities and Regional Variation in Colorectal

Cancer Survival in Finland

Isabelle Finke 1, 2; Karri Seppä 3; Nea Malila 3; Lina Jansen 1;

Hermann Brenner 1, 4, 5; Janne Pitkäniemi 6, 7

1Division of Clinical Epidemiology and Aging Research, German Cancer

Research Center (DKFZ), Heidelberg, Deutschland

2Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Deutschland

3Finnish Cancer Registry, Helsinki, Finnland

4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and

National Center for Tumor Diseases (NCT), Heidelberg, Deutschland

5German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

6Department of Public Health, University of Helsinki, Helsinki, Finnland

7Faculty of Social Sciences, University of Tampere, Tampere, Finnland

Purpose: Previous studies reported lower colorectal cancer (CRC) sur-

vival in patients with lower educational levels. We investigated the impact

of regional variation on educational inequalities in CRC survival by using

both individual and aggregated area-based information on education.

Methods: Patients diagnosed with colorectal cancer (ICD-10 C18-20) in Fin-

land in 2007-2016 were followed up for death until end of 2016. Age-stan-

dardized relative survival and relative excess risk of death (RER) were es-

timated by sex using the period approach (Ederer II). RERs were adjusted

for follow-up time, age, stage at diagnosis, cancer site, urbanity and region

by using piecewise constant Poisson excess hazard models. All analyses were

conducted separately including individual (basic, secondary, high) and ag-

gregated area-based (quartiles Q1-Q4 based on the proportion of population

with basic education) information on education, respectively.

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2018

Index

2018

Results: Altogether 24,462 CRC patients diagnosed in 2007–2016 were

included in the analyses. ere was a clear gradient in 5-year relative sur-

vival across education groups (Men: Basic 61%, Secondary 64%, High

68%; Women: Basic 61%, Secondary 68%, High 71%). Compared to the

basic education group, RER in the high education group was 0.73 (95%

Condence Interval (CI) 0.65–0.82) in men and 0.67 (95% CI 0.59–0.76)

in women. Accounting for regional variation had no eect on the RERs,

but the eects were slightly attenuated when stage was adjusted for (RER

0.77 in men and 0.69 in women with high education). No association be-

tween area-based education and 5-year relative survival in men (Q1 63%,

Q2 64%, Q3 65%, Q4 63%) and women (Q1 61%, Q2 67%, Q3 69%, Q4

65%) was observed.

Conclusions: Educational inequalities in CRC survival are still present

in Finland and could not be explained by regional variations neither for

individual nor area-based education. Individual education information

should be preferred over area-based if interested in survival dierences

by education.

Disclosure Statement: e authors declare no conict of interest.

617

Record Linkage of 76,026 Cancer Cases Notied by Death

Certicate Only

Benjamin Barnes; Klaus Kraywinkel

Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland

Purpose: e federal cancer registry data act tasks the Robert Koch In-

stitute (RKI) with conducting an interstate data linkage to identify indi-

vidual cases reported by multiple epidemiological registries. e linkage

uses pseudonym control numbers based on patient names and dates of

birth. Because not all registries send control numbers to the RKI; a na-

tionwide linkage has not yet been possible. Methods: e current linkage

focused on matching cases notied by death certicate only (DCO cases)

in the years 2014 and 2015 with previously diagnosed cases. Data from 12

federal states covering 77% of the population were included. Due to the

limited identifying information available; a probabilistic approach was ap-

plied to identify likely matches. Results: A total of 76;026 DCO cases were

linked with approximately 8.5 million other cases. Of these DCO cases;

421 (0.6%) were identied as likely matches. Niedersachsen had the larg-

est proportion of likely matched DCO cases (1.4%). Analyses by county

(Landkreis) suggested particularly large numbers of likely matches in Ber-

lin and at the border between Lower Saxony and North Rhine-Westphalia.

Considering these cases as duplicates would reduce the estimated total

cancer incidence in Germany by far less than one percent. Conclusions:

Although the identication and elimination of duplicate records has only

a small impact on nationwide statistics; regional analyses – particularly at

state borders – may be aected to a greater extent. By focusing on DCO

cases; not only can duplicate records be identied; but vital status can be

updated for survival analyses.

620

Socioeconomic Deprivation and Burden of Cancer

in Baden-Württemberg

Volker Arndt 1, 2; Silke Hermann 1; Susanne Bergbold 1

1Deutsches Krebsforschungszentrum Heidelberg, Epidemiologisches

Krebsregister Baden-Württemberg, Heidelberg, Deutschland

2Deutsches Krebsforschungszentrum Heidelberg, Unit of Cancer Survivorship,

Heidelberg, Deutschland

Purpose: Socioeconomic disparity (SD) has been linked to dierences in

access to health care, cancer incidence, mortality, and prognosis but the

association between SD and stage at diagnosis is less well established [1-5].

Methods: Data from the Cancer Registry Baden-Württemberg on newly

diagnosed primary cancers between 2011 and 2017 were linked with com-

munity level SD from the German Index of Socioeconomic Deprivation

[6]. Dierences in cancer incidence were analyzed using multilevel Pois-

son regression models, in stage distribution (regional/distant vs. local/

in-situ) using chi²-test, and in age-adjusted survival using Cox propor-

tional hazards model with and without stage adjustment.

Results: Overall, there was a negative association between cancer inci-

dence and socioeconomic deprivation, i.e. lower rates were observed in

more deprived areas. is pattern was mostly pronounced for melanoma

and female breast cancer. Higher rates in more deprived areas were ob-

served for stomach cancer (males). e proportion of advanced tumors

was higher in socially more deprived areas for melanoma, colorectal

(males), breast and prostate cancer. Case fatality was higher in socially

more deprived areas for all cancers combined. Site and sex specic anal-

ysis revealed higher case fatality rates in more deprived areas for melano-

ma, stomach, prostate and thyroid cancer in males and for breast cancer

in females. Dierences in survival disappeared aer adjustment for dier-

ences in stage distribution.

Conclusions: Stage-adjusted prognosis does not vary according to so-

cioeconomic deprivation in Baden-Württemberg. e dierences in can-

cer incidence and stage distribution are most likely due to dierences in

screening behavior.

References:

1. Hoebel J et al. Front Oncol 2018; 8: 402

2. Hartung TJ, Johansen C. Forum 2017; 32: 318-23

3. Jansen L et al. Int J Cancer 2014; 134: 2951-60

4. Kuznetsov L et al. Int J Public Health 2012; 57: 827-35

5. Eberle A et al. J Public Health 2010; 18: 227-35

6. Kroll LE et al. J Health Monitoring 2017; 2: 103-20

Disclosure Statement: Nothing to disclose.

645

Human Papillomavirus Infections (HPV) in Young Women Ten

Years after the Introduction of HPV Vaccination in Germany:

The Nation-Wide HPV Prevalence Study

Viktoria Schönfeld 1; Adine Marquis 1; Sarah Thies 2; Amrei Krings 1;

Miriam Wiese-Posselt 1; Ole Wichmann 1; Andreas Kaufmann 2;

Thomas Harder 1

1Robert Koch-Institut, Infektionsepidemiologie, Berlin, Deutschland

2Charité Universitätsmedizin, Frauenklinik, Berlin

Purpose: Persisting infections with high-risk human papillomavirus

(HPV) can lead to cervical cancer. In 2007, routine HPV vaccination of

girls was introduced into the national vaccination schedule in Germany.

Vaccine coverage reached 44.6% in 2016. e two HPV vaccines on the

German market confer protection against two or seven high-risk HPV

types. Aim of our study was to investigate HPV prevalence in women aged

20-25 years and to estimate the eects of HPV vaccination ten years aer

the introduction of HPV vaccination.

Methods: We performed a nation-wide representative cross-sectional

study in 2017-18 using a two-step stratied sampling design to recruit

at least 1,173 women aged 20-25 years from population registries in

Germany. Participants used self-sampling kits (Evalyn brush; Rovers,

Oss, e Netherlands) to collect cervico-vaginal samples and completed

questionnaires. Samples were tested for 18 high-risk and eight low-risk

HPV types (genotyping HPV test; Optiplex; Diamex, Heidelberg).

Results: In 1,202 of 1,226 study participants HPV test results as well as

data on sociodemographic characteristics and HPV vaccination status

were available. Overall response rate was 15%, ranging from 10 to 18%

locally. Of 1,134 participants, 597 (53%) had received a full course of HPV

vaccine. Further analyses on HPV type prevalence and vaccine eective-

ness are in preparation and will be presented at the conference.

Conclusions: Our study will generate estimates of HPV type distribution

and assess the impact of HPV vaccination in Germany. ese data will

contribute to the evaluation of the national vaccination strategy and im-

prove prevention of HPV-associated carcinoma in Germany (supported

by BMG; grant no. 321-4471-02/158).

Disclosure Statement: All authors have nothing to disclose.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 47

Inhalt

2018

Index

2018

Gastrointestinal (Colorectal) Cancer

Best-of-Abstracts-Vorträge

533

High Microsatellite Instability (MSI-H) is Associated with

Distinct Clinical and Molecular Characteristics and an

Improved Survival in Early Colon Cancer (CC): Real Life Data

from the AIO Molecular Registry Colopredict Plus

Stefanie Nöpel-Dünnebacke 1; Hendrik Jütte 2; Celine Lugnier 1;

Dirk Arnold 3; Nadezhda Basara 4; T Dahm 1; Inke Feder 2; Wolfgang Hiller 5;

Torsten Herzog 6; Renate Klaassen-Mielke 7; Lothar Müller 8; Metin Senkal 9;

Gabriele Siegler 10; Christian Teschendorf 11; Guido Trenn 12;

Berlinda Verdoodt 2; Heiner Wolters 13; Waldemar Uhl 6;

Anke Reinacher-Schick 1; Andrea Tannapfel 2

1Abteilung für Hämatologie, Onkologie und Palliativmedizin, St. Josef Hospital

Bochum, Bochum, Deutschland

2Institut für Pathologie, Ruhr-Universität Bochum, Bochum

3Onkologie mit Sektion Hämatologie, Asklepios Klinikum Altona Hamburg,

Hamburg

4Medizinische Klinik 1, Malteser Krankenhaus St. Franziskus-Hospital, Flensburg

5Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Lippe GmbH,

Detmold

6Klinik für Allgemein- und Viszeralchirurgie, St. Josef Hospital Bochum, Bochum

7ABTEILUNG FÜR MEDIZINISCHE INFORMATIK, BIOMETRIE UND EPIDEMIOLOGIE,

Ruhr-Universität Bochum

8Onkologie UnterEms, Leer

9Klinik für Allgemein- und Viszeralchirurgie , Marien Hospital Witten , Witten

10Klinikum Nürnberg, Klinik für Innere Medizin 5, Nürnberg

11Klinik für Innere Medizin I, St. Josef Hospital Dortmund, Dortmund

12Klinik für Innere Medizin I, Knappschaftskrankenhaus Bottrop, Bottrop

13Klinik für Allgemein- und Viszeralchirurgie, St. Josef Hospital Dortmund,

Dortmund

Purpose: MSI-H is a known positive prognostic factor in early CC ob-

served retrospectively in numerous clinical trials. A prospective valida-

tion in real life cohorts, also compared to other molecular and clinical

factors, is still lacking.

Methods: From Sep 2013 to Jan 2019 patients (pts.) with UICC stage II/III

CC were registered in 70 German cancer centers. MS status was tested by

immunohistochemistry (IHC) of mismatch repair proteins. Loss of pro-

tein expression was conrmed by fragment length analysis (FLA) den-

ing MSI-H and MSS tumors. Mutational status in RAS, BRAF, PI3K was

determined by next generation sequencing (NGS). Disease free survival

(DFS) and overall survival (OS) were estimated using COX regression.

Relapse rates (RR) were calculated as a percentage of the subgroup.

Results: Tissue of 1787 pts. was analyzed by IHC and NGS. 423 pts. were

MSI-H upon FLA (23.7%). Association of MS status with clinical and mo-

lecular factors is shown in Table 1. Rate of MSI-H increased with age with

BRAF mutations (MT) more oen detectable in older MSI-H pts. (%BRAF

MT ≤70/70-75/>75y: 16.9/ 19.2/63.9%). DFS was signicantly longer in

MSI-H versus (vs.) MSS pts. (hazard ratio (HR) 0.702; condence interval

(CI) 0.547-0.900; p=0.005), while the HR for OS was not signicant due

to few events recorded (0.781; CI 0.595-1.0x26; p=0.076). DFS/OS in right

vs. le sided primary tumors were not dierent (HR 1.003 CI 0.844-1.192;

p=0.971/ HR 1.134; CI 0.930-1.383; p=0.213). In the BRAF MT subgroup,

RR was substantially lower in MSI-H vs. MSS pts. (5.2/19.7%) albeit RR in

MSI-H pts. did not dier between BRAF MT/WT (3.5/3.2%).

Conclusions: MSI-H tumors were more frequently detected in our cohort

compared to reported data, presumably related to the older age of our pts.

e high incidence of BRAF MT point to a sporadic etiology of most cas-

es. We could also conrm MSI-H as a strong prognostic marker in early

CC independent of BRAF MT.

Disclosure Statement: e authors state no disclosures.

Vorträge

678

Longitudinal Investigation of Circulating Tumour Cells

in Liquid Biopsies of Colorectal Cancer Patients - Analysis

of the Clinical Benet of a New Biomarker of Tumour Burden

and Relapse

Alexander Hendricks 1; Katharina Dall 2; Reinhild Geisen 3;

Christian Roeder 3; Susanne Sebens 3; Thomas Becker 2;

Clemens Schafmayer 1; Sebastian Hinz 1

1Universitätsmedizin Rostock, Klinik für Allgemeine-, Viszeral- und

Transplantationschirurgie, Rostock, Deutschland

2UKSH Campus Kiel, Klinik für Allgemeine- Viszeral- und Thoraxchirurgie, Kiel,

Deutschland

3Christian Albrechts Universität Kiel, Institut für Experimentelle

Tumorforschung, Kiel, Deutschland

Purpose: Previously, we established a semi-quantitative RT-PCR against

CK20 and were able to identify colorectal cancer (CRC) patients at risk.

Ongoing to this work, we now want to report on our recent longitudinal

data on serial CK20 mRNA analysis of CRC patients. For the rst time

this allows us to monitor the burden of the CTC over a course of time and

especially aer surgery and absence of the tumour.

Methods: In total 126 serial blood samples from 50 patients were anal-

ysed. Blood was drawn prior to surgery (t0), one month (t1), three (t2), six

(t3), nine (t4) and twelve months (t5) aer surgery. Blood samples were

analysed by CK20 RT-PCR. e PCR data was assessed regarding the pre-

viously published clinically relevant cut o value.

Results: At t0 17 (34.0%) patients were above the cut-o. At t1 a signif-

icant decrease of the CTC load was monitored (p<0.001). Also, at t2, t3

and t4 less CTC were measured (p=0.015, p<0.001, p=0.019, respectively).

ese results show, that the CTC load does correlate with the tumour bur-

den – aer macroscopically tumour free resection, the CTC load decreas-

es as no more tumorous tissue enables the release of CTC.

Analysing individual patients we exemplarily identied two patients. (A)

Stage II sigmoid carcinoma. Ongoing increase of mRNA expression over

the postoperative course of 12 months. At t6 the cut-o was passed. 14

months aer surgery a local relapse was diagnosed. (B) Stage III sigmoid

carcinoma. Adjuvant treatment was started. No elevated CTC in the rst

blood sample. T2: signicant increase of CTC passed the cut-o. Six

months postoperative, iliacal CRC metastasis.

Conclusions: We successfully implemented a protocol of obtaining and

analysing serial blood samples as liquid biopsies. By this, we might be able

to identify CRC patients who potentially benet of a more thorough aer-

care at an earlier stage of follow-up. e detection of CK20-positive CTC

may be a promising tool to detect a tumour recurrence prior to routine

radiological diagnostics.

Disclosure Statement: No conict of interest.

749

Laparoscopic and Open Resection of Rectal Cancer—is Age an

Eect Modier for Short- and Long-Term Survival?

Teresa Draeger 1, 2; Vinzenz Völkel 1, 2; Michael Gerken 1; Alois Fürst 1;

Monika Klinkhammer-Schalke 1

1Caritas Krankenhaus St. Josef, Regensburg, Deutschland

2Tumorzentrum Regensburg, Regensburg, Deutschland

Purpose: Various studies proofed the oncologic safety of laparoscopic

resection of rectal carcinoma. However, there does not exist a clear rec-

ommendation on whether age should inuence the choice of the surgical

approach.

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Inhalt

2018

Index

2018

Methods: is population-based retrospective cohort study compares

outcomes of laparoscopic and open surgery in rectal cancer patients.

Perioperative mortality, 5-year overall, relative, and recurrence-free sur-

vival rates were analyzed separately for three age groups (< 60 years, 60–69

years, 70–79 years). Data originate from 30 regional German cancer reg-

istries that cover approximately one quarter of the German population.

All primary nonmetastatic rectal adenocarcinoma cases with surgery

between 2005 and 2014 were eligible for inclusion. To compare survival

rates, Kaplan–Meier analysis, a relative survival model, and multivariable

Cox regression were used; a sensitivity analysis assessed bias by exclusion.

Results: 10,754 patients fullling all inclusion criteria without missing data in

important variables were included in the analysis. e mean laparoscopy rate

was 23.0% and increased over time. Uni- and multivariable regression anal-

ysis of 30-day postoperative mortality revealed advantages for laparoscopi-

cally treated patients, although the signicance level was not reached in any

age group (for age group 70–79, it was missed only slightly: odds ratio, OR

0.559; 95% condence interval, 95% CI 0.296–1.058). Regarding 5-year over-

all survival, laparoscopy generally seems to be the superior approach, whereas

for recurrence-free survival patients under 60 years beneted more from the

minimally invasive approach than older patients (< 60 years: hazard ratio, HR

0.703, 60–69 years: HR 0.787, 70–79 years: HR 0.923).

Conclusions: Laparoscopy shows similar results to the open approach in

terms of postoperative mortality in all age groups. Concerning long-term

outcomes, younger patients benetted most from the minimally invasive

approach. Increased use of laparoscopy for rectal cancer should be con-

sidered in this group.

756

Somatic Alterations and Tumor Mutational Burden (TMB) in

Patients with Metastatic Colorectal Cancer (mCRC) Treated

with FOLFiRI Plus Bevacizumab or Cetuximab (Fire-3 Trial)

Arndt Stahler 1; Sebastian Stintzing 2; Jobst C. von Einem 2;

C. Benedikt Westphalen 1; Nicole Krämer 3; Marlies Michl 1;

Dominik Paul Modest 2; Ludwig Fischer von Weikersthal 4; Thomas Decker 5;

Alexander Kiani 6; Tobias Heintges 7; Christoph Kahl 8; Frank Kullmann 9;

Werner Scheithauer 10; Markus Möhler 11; Ursula Vehling-Kaiser 12;

Thomas Kirchner 13; Andreas Jung 13; Volker Heinemann 1

1Klinikum der Universität München, Medizinische Klinik III, München,

Deutschland

2Charite - Campus Mitte, Medizinische Klinik mit Schwerpunkt Hämatologie

und Onkologie CCM, Berlin, Deutschland

3STABURO Statistical Consulting GmbH, München, Deutschland

4Klinikum St. Marien, Onkologie, Amberg, Deutschland

5Onkologische Praxis Prof. Dr. med. Thomas Decker, Ravensburg, Deutschland

6Klinikum Bayreuth GmbH, Medizinische Klinik IV, Bayreuth, Deutschland

7Rheinland Klinikum Neuss GmbH - Lukaskrankenhaus, Medizinische Klinik II,

Neuss, Deutschland

8Klinikum Magdeburg gemeinnützige GmbH, Abteilung für Hämatologie,

Onkologie und Palliativmedizin, Magdeburg, Deutschland

9Klinikum Weiden, Medizinische Klinik I, Weiden in der Oberpfalz, Deutschland

10Medizinische Universität Wien, Medizinische Klinik I & CCC, Wien, Österreich

11Universitätsmedizin Mainz, Medizinische Klinik I, Mainz, Deutschland

12Onkologische Praxis Dr. Ursula Vehling-Kaiser, Landshut, Deutschland

13Ludwig-Maximilian-Universität München, Pathologisches Institut, München,

Deutschland

Purpose: Molecular biomarkers and primary tumor sidedness guide

treatment decisions in mCRC. Precision oncology is a novel model to

identify targetable alterations and TMB.

Methods: FoundationOne® next generation sequencing (NGS) identied

single nucleotide variants (SNV), copy number alterations (CNA), TMB

and microsatellite instability (MSI-H) in patients treated in FIRE-3. Data

was correlated with overall response (OR), progression free survival (PFS)

and overall survival (OS). Multivariate regression analyses conrmed

prognostic and predictive biomarkers for OR.

Results: 373 of 754 patients (49.4 %) provided eligible material for this

analysis. Frequent known SNVs were found in TP53 (72.4 %), APC (66.0

%), KRAS (27.3 %), PIK3CA (16.1 %), BRAF (12.1 %), SMAD4 (8.0 %),

FBXW7 (7.0 %), frequent CNAs were found in FLT3 (5.6 %) and MYC

(6.7 %). RAS wildtype (WT) had signicantly longer OS (27.9 vs. 20.6

months, HR = 0.62 [95% CI 0.50 – 0.78], p = 0.0001) and PFS (10.4 vs

8.9 months, HR = 0.75 [95% CI 0.60 – 0.94], p = 0.01) compared to RAS

mutant (MUT) patients. OS (26.4 vs. 15.9 months, HR = 0.57 [95% CI

0.41 – 0.80], p = 0.001) and PFS (10.5 months vs 7.6 months, HR = 0.62

[95% CI 0.45 – 0.85], p = 0.003) were longer in BRAF WT vs. MUT pa-

tients. SMAD4 WT vs. MUT patients showed signicantly longer OS (HR

= 0.59 [95% CI 0.34 – 1.01], p = 0.05) and higher probability of response

[odds ratio SMAD4 SV vs. WT = 0.32 [95% CI 0.10 – 0.98], p = 0.05]

when treated with cetuximab. Multivariate regression conrmed BRAF,

KRAS and SMAD4 SNV as prognostic biomarkers and KRAS and SMAD4

MUT as predictive biomarkers for OR. High TMB (> 8 mutations / MB)

and MSI-H were detected in 56 and 10 patients, respectively, and showed

a trend towards better OR in patients receiving cetuximab.

Conclusions: RAS, BRAF and SMAD4 MUT were identied as poor prog-

nostic biomarkers in patients of FIRE-3. SMAD4 MUT might provide pre-

dictive relevance for cetuximab ecacy.

Poster

Dissemination of Intestinal Epithelial Cells in Inammation-

Associated-Colorectal- Carcinogenesis

Johanna Born 1; Alexander Hendricks 2; Alexander Bernsmeier 3;

Sascha Rahn 1; Christian Röder 1; Susanne Sebens 1

1Institut für experimentelle Tumorforschung, Christian-Albrechts-Universität zu

Kiel, Kiel, Deutschland

2Klinik für Allgemeine, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie,

UNIVERSITÄTSKLINIKUM Schleswig-Holstein, Kiel, Deutschland

3Sektion klinische Transplantation Klinik für Allgemeine, Viszeral-, Thorax-,

Transplantations- und Kinderchirurgie, UNIVERSITÄTSKLINIKUM Schleswig-

Holstein, Kiel, Deutschland

Purpose: Cellular markers for the detection of circulating tumor cells

(CTC) in patients with colorectal carcinoma (CRC) have been shown to

have a high predictive and prognostic relevance. Patients suering from

inammatory bowel diseases (IBD) have an increased risk to develop

colorectal cancer particularly aer long duration of disease. us, this

study investigated whether markers used for CTC detection in CRC

patients can be already determined in blood of IBD patients. Moreover,

detection levels were correlated with clinicopathological data such as

severity of inammation.

Methods: CK20, PLS3, LAD1, DEFA5 -mRNA expression was analyzed

by qRT-PCR in total RNA from peripheral blood mononuclear cell frac-

tion from patient blood samples provided by the biobank of Comprehen-

sive Cancer Center Kiel, Germany. In order to model the impact of an

inammatory microenvironment on malignancy-associated alterations

and expression of CTC markers, the intestinal epithelial cell line NCM-

460 was indirectly co-cultured with primary M1-like polarized human

macrophages in vitro.

Results: Markers used for CTC detection in CRC patients (n=100), par-

ticularly CK20 and PLS3, were also elevated in IBD patients (n=75) com-

pared to healthy donors (n=40). No dierence could be seen in the levels

of these markers in CRC or IBD patients. Current statistical analysis aims

at identifying a correlation between detection levels and clinical parame-

ters. Results from the in vitro co-culture system indicate that proinam-

matory macrophages inuence CTC marker expression as well as foster a

motile and mesenchymal phenotype in NCM-460 cells.

Conclusions: ese data suggest that dissemination of intestinal epithe-

lial cells into the blood is promoted by inammation and occurs already

in IBD patients. Further analyses are needed to understand the role and

evaluate the prognostic value of these CTC markers in IBD patients.

Disclosure Statement: e Authors declare no conict of interest.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 49

Inhalt

2018

Index

2018

130

The Inuence of Postoperative Complications on Long-Term

Prognosis in Patients with Colorectal Carcinomas

Clemens Beck 1; Vera Schellerer 1; Klaus Weber 1; Maximilian Brunner 1;

Abbas Agaimy 2; Sabine Semrau 3; Robert Grützmann 1; Susanne Merkel 1

1Universitätsklinikum Erlangen, Chirurgie, Erlangen, Deutschland

2Pathologisches Institut, Universitätsklinikum Erlangen, Erlangen, Deutschland

3Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland

Purpose: e impact of postoperative complications (POCs) on long-

term prognosis in patients with colorectal carcinomas was analyzed with

respect to the severity of complications according to the Clavien-Dindo

classication (CDC).

Methods: e data of 2158 consecutive patients with curative elective

resection of a colorectal carcinoma (CME or TME/PME) without

distant metastases between 1995 and 2014 were analyzed. POCs were

documented in a standardized form and retrospectively assigned to

the CDC. Patients who died postoperatively (CDC grade V, 1.7%) were

excluded. e inuence of CDC on locoregional and distant recurrence,

disease-free and overall survival was examined.

Results: 990 patients with colon carcinoma and 1168 with rectal car-

cinoma were analyzed. 467 patients (21.6%) had POCs: CDC I 141

(6.5%), CDC II (pharmacological treatment) 162 (7.5%), CDC III

(surgical, endoscopical or radiological intervention) 112 (5.2%) and

CDC IV (intensive care) 52 (2.4%). A higher rate of POCs and a high-

er grade of CDC were found in men, ASA III-IV patients, rectal car-

cinomas, abdominoperineal excisions and multivisceral resections.

e 5-year rate of locoregional recurrences was 5.6% and was highest in

CDC grade III patients (12.9%). e 5-year rate of distant metastases was

16.7% and increased continuously to 23.7% in CDC grade IV patients. In

disease-free survival, the 5-year rate was 73.4% and decreased to 55.4%

in CDC IV patients. In overall survival, the 5-year rate was 81.3% and

decreased to 63.1% in CDC IV patients. is was conrmed in multi-

variate Cox regression analysis. We found a signicantly higher risk for

locoregional recurrences (HR 2.2; p=0.005) and distant metastases (1.7;

p=0.020) in CDC III patients, while patients with CDC grade IV were

associated with signicantly worse disease-free (HR 1.8; p=0.002) and

overall survival (HR 1.9; p=0.001).

Conclusions: Patients with POCs aer colorectal surgery have worse

long-term prognosis. With increasing CDC grade, survival deteriorates.

Disclosure Statement: e authors declare no conict of interest.

131

The Inuence of Body Mass Index on Long-Term Prognosis

in Patients with Colon Carcinomas

Susanne Merkel 1; Julian Fuchs 1; Vera Schellerer 1; Maximilian Brunner 1;

Carol Geppert 2; Robert Grützmann 1; Klaus Weber 1

1Universitätsklinikum Erlangen, Chirurgie, Erlangen, Deutschland

2Universitätsklinikum Erlangen, Pathologisches institut, Erlangen, Deutschland

Purpose: Obesity is an established risk factor for a number of chronic

diseases, including diabetes, cardiovascular diseases and cancer with an

unfavorable inuence on life expectancy. A crude measure of obesity is the

body mass index (BMI). Here, we analyze the impact of the preoperative

BMI on long-term prognosis in patients with colon carcinomas.

Methods: e data of 694 consecutive patients with curative resection of a

colon carcinoma (CME, complete mesocolic excision), no distant metas-

tases, between 2003 and 2014 were analyzed. BMI was categorized accord-

ing to the proposal of the WHO: <18.5 underweight, 18.5-24.9 normal

weight, 25.0-29.9 overweight, ≥30.0 obesity.

Results: 13 patients (1.9%) were underweight, 221 patients (31.8%) were

normal weight, 309 patients (44.5%) were overweight and 151 patients

(21.8%) were obese. Men were found to be signicantly more frequently

overweight or obese (p<0.001). e 5-year rate of locoregional recurrences

was 2.1%, no inuence of any risk factor including BMI was found. e 5-year

rate of distant metastases was 13.4%. It was signicantly higher in advanced

stage and emergency patients, but was not inuenced by the patients’ BMI.

e 5-year rate of disease-free survival was 72.4%, the 5-year rate of over-

all survival was 78.1%. Both were signicantly inuenced by age, ASA

classication, emergency presentation, tumor site, stage and preoperative

BMI. Obese patients had a signicantly better 5-year disease free surviv-

al than normal weight patients (78.5% vs 69.8%; p=0.045). is could be

conrmed in multivariate Cox regression analysis (HR 0.7; p=0.034). In

addition, obese patients had a signicantly better overall survival than

normal weight patients (82.4% vs 73.4%; p=0.027), which also could be

conrmed in multivariate Cox regression analysis (HR 0.6; p=0.019).

Conclusions: In a cohort of 694 colon carcinoma patients treated with

CME, obese patients at the time of surgery were not found to have worse

prognosis than normal weight patients.

Disclosure Statement: e authors declare no conict of interest.

223

Prognostic Value of BRAF, KRAS and MSI Status in Patients

with Advanced Left- and Right-Sided Colorectal Cancer: A

Retrospective Evaluation Based on Data from the Tumor

Documentation of the UCT Frankfurt

Maximilian Stohner 1; Corinna Bendfeldt 1; Gabriele Husmann 1;

Wolf O. Bechstein 2; Peter Wild 3; Stefan Zeuzem 4; Jörg Trojan 4;

Christine Koch 4; Ursula Pession 2; Christian Brandts 5

1Universitätsklinikum Frankfurt, Universitäres Centrum für Tumorerkrankungen:

Tumordokumentation, Frankfurt, Deutschland

2Universitätsklinikum Frankfurt, Zentrum der Chirurgie: Klinik für Allgemein-

und Viszeralchirurgie, Frankfurt, Deutschland

3Universitätsklinikum Frankfurt, Senckenberg Institut für Pathologie, Frankfurt,

Deutschland

4Universitätsklinikum Frankfurt, Zentrum der Inneren Medizin: Medizinische

Klinik I, Frankfurt, Deutschland

5Universitätsklinikum Frankfurt, Universitäres Centrum für Tumorerkrankungen,

Frankfurt, Deutschland

Purpose: In recent years, a large number of studies have dealt with the

prognostic dierence between advanced le- and right-sided colorectal

cancer (CRC). It became clear that patients with le-sided primarius have

a higher survival probability. Further studies linking certain molecular

markers such as KRAS, BRAF or MSI to the location showed an increase

in mutations on the right side. is issue will be further investigated using

data from the tumor documentation of the UCT Frankfurt.

Methods: For our study, we considered routine data from the UCT tu-

mor documentation on patients with advanced CRC (ICD-10 C18-20,

UICC III/IV) from 2008 until July 2019. We assigned exura linealis, co-

lon descendens, colon sigmoideum and rectum to the group of le-sided

carcinomas; caecum, appendix, colon ascendens, exura hepatica, colon

transversum were assigned to the right-sided tumors. Endpoint was the

overall survival aer 5 years (OS).

Results: 612 (78 %; total: 785) had a primary tumor on the le side. OS

was determined for patients with le-sided CRC at a rate of 47.2 % (95

% CI: 0.41 to 0.53), for patients with right-sided CRC at a rate of 37,2 %

(95 % CI: 0.28 to 0.46). In general, mutations could be detected more fre-

quently in the right-sided tumors. e survival could only be determined

in patients with mutated KRAS due to the small number of cases. ere

was no signicant dierence between le and right side.

Conclusions: As already proven in various other sources, the data of the

UCT tumor documentation also conrms the better prognosis for pa-

tients with le-sided CRC. As our results show, this could be associated

with a lower mutation rate compared to right-sided tumors. To conrm

this theory and for a more meaningful evaluation of the survival time of

the individual mutations, a further study with an increased number of

cases will be added.

References:

1. Petrelli, F. et al.: JAMA Oncol. 2017;3(2):211-219.

2. Sinicrope, F.A. et al.: JAMA Oncol. 2017;3(4):472-480

Disclosure Statement: All authors have declared no conicts of interest.

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264

Farkor: Evaluating a Screenig Program for Familial Colorectal

Cancer Risk

Sabine Homann 1; Alexander Crispin 1; Doris Lindörfer 1; Gaby

Sroczynski 2; Uwe Siebert 2; Ulrich Mansmann 1; Farkor Konsortium 3

1Institut für Medizinische Informationsverarbeitung, Biometrie und

Epidemiologie, Ludwig Maximilian‘s Universität, München, Deutschland

2Institut für Public Health, Medical Decision Making und HTA, Tiroler

Privatuniversität UMIT, Hall, Österreich

3Kassenärztliche Vereinigung Bayerns, München, Deutschland

Purpose: Colorectal cancer (CRC) screening in Germany starts at age 50.

As there is evidence that individuals with a family history of CRC have an

increased risk of developing CRC before age 50, screening for this group

should start earlier. is study evaluates the clinical and economic eects

of a risk-adapted screening program for CRC in individuals between 25

and 50 years of age.

Methods: An interim analysis assess the eects of the screening program

FARKOR (Family Related Colorectal cancer Risk) in a population-based

prospective cohort study. e program is open to members of the statu-

tory health insurance in Bavaria between October 2018 and March 2020.

Participants enter the study through their physicians or a public cam-

paign. Additionally, insurances contact patients recently diagnosed with

CRC to inform them that their relatives may have an increased risk of

developing CRC. Trained doctors classify participants as potential risk

carriers or as inconspicuous. Potential risk carriers are invited to a shared

decision making shared decision making on 1) immunological test for

fecal occult blood or 2) colonoscopy. Assessment of long-term benets,

harms and cost-eectiveness of FARKOR uses decision-analytic modeling

from the perspective of the German health care system.

Results: Aer 11 months, 4823 patients have joined the program. Among

the 1675 identied potential risk carriers, 1201 participated in a shared

decision making aer which 421 (635) decided to undergo an immuno-

logical test for fecal occult blood (colonoscopy). Adenoma were detected

in 17% of screening colonoscopies. No complication occurred.

Conclusions: e preliminary results of an interim analysis suggest good

adherence to the proposed screening measures. Further evaluations will

follow to assess its overall clinical and economic eects.

Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-

mittee (G-BA) supports this work: 01NVF17026. e author declare no conict of

interest.

341

IVOPAK II Study: Morbidity Following Secondary Resection

of Colorectal Liver Metastases

Vera Schellerer 1; Susanne Merkel 1; Robert Grützmann 1;

Stephan Kersting 1; Axel Wein 2

1Chirurgische Klinik des Universitätsklinikums Erlangen, Erlangen, Deutschland

2Medizinische Klinik 1- Gastroenterologie, Pneumologie und Endokrinologie

des Uni-Klinikums Erlangen, Erlangen, Deutschland

Purpose: In the IVOPAK II study, patients with unresectable metastatic

colorectal carcinoma (CRC) receiving palliative chemotherapy and bio-

logical agents aer expanded RAS-analysis are regularly re-staged by im-

aging with subsequent tumor board decision every 2 months to identify

patients becoming secondary resectable.

Methods: Between 7/2016 and 7/2019, 40 patients were included into the

study. 50% (n=20) had a RAS mutation, 50% (n=20) an All-RAS-wildtype.

To date, 14 patients received a secondary curative therapy, including 9 pa-

tients with liver metastases only (HEP), 1 patient with resection of HEP

and primary tumor (PT), 2 patients with resection of HEP and pulmonary

metastases (PUL) and PT, 1 patient with resection of PUL, 1 patient with

peritoneal metastases.

Results: Median age of the 12 patients with HEP was 65 years (range:

56-72), including 10 men and 2 women. RAS wildtype was diagnosed in

67% (n=8), RAS mutations in 33% (n=4). Patients underwent secondary

curative surgery in median 6 months aer starting palliative treatment

(range 3-18). e 12 patients with HEP (+/- PUL) were treated by surgical

resection (n=7), radiofrequency ablation (n=3), both (n=2). Liver resec-

tions included 2 atypical and 4 segmental resections, 2 right hemihepatec-

tomies and 1 extended right hemihepatectomy. Postoperatively, the fol-

lowing complications occurred in liver-resected patients (Clavien-Dindo

classication): Grade 0 (n=2), Grade I (n=1), Grade II (n=1), Grade III

(n=2), Grade III (n=3). Median follow-up of the 12 patients is currently

6 months (0-28). 11 of 12 patients are still alive. 4 patients (30%) remain

with no evidence of disease.

Conclusions: Even in patients with unresectable metastatic CRC receiv-

ing palliative therapy, regularly restaging for evaluation of secondary cu-

rative treatment options is meaningful. e high response rate of All-RAS

wildtype population is important for secondary resection.

Disclosure Statement: e authors declare no conict of interest.

348

Case of Two Patients with MSI-High Metastatic Colorectal

Cancer Treated with Pembrolizumab

Annika Kurreck 1; Sebastian Stintzing 2; Dominik Paul Modest 1; Ivan Jelas 3;

Jobst C. von Einem 2

1Charité University Medicine Berlin, Department of Hematology, Oncology, and

Tumorimmunology (CVK), Berlin, Deutschland

2Charité University Medicine Berlin, Department of Hematology and Oncology

(CCM), Berlin, Deutschland

3Charité University Medicine Berlin, Charité Comprehensive Cancer Center,

Berlin, Deutschland

Purpose: Immune checkpoint inhibitors (ICI) have become a standard

treatment in everyday oncological practice. In clinical trials, pembroli-

zumab and nivolumab as well as the combination of nivolumab and

ipilimumab have demonstrated ecacy in patients with microsatellite

instability-high (MSI-high) metastatic colorectal cancer (mCRC). e

underlying mismatch repair deciency seems to correlate with the lev-

el of neoantigen and consecutively with high immunogenicity- this may

explain the treatment eect derived from ICI in MSI-high mCRC. Unlike

the FDA, the EMA has not yet approved ICI for the treatment of MSI-

high mCRC.

Methods: We present a scientic report on the clinical courses of two

male patients with RAS-wildtype, MSI-high mCRC, who received o-la-

bel pembrolizumab (200 mg every 3 weeks) in our department aer fail-

ure to rst- and third-line treatment, respectively.

Results: A 42-year old patient with synchronous hepatic mCRC received

pembrolizumab aer tumor progress to rst-line treatment with FOLFI-

RI and Cetuximab. e patient developed signicant clinical symptoms

and corresponding radiological tumor progression aer four administra-

tions of ICI. We administered pembrolizumab as fourth-line treatment to

another 49-year old patient with mCRC, that metastasized per continui-

tatem to the right-sided thoracic wall. Aer three applications, a CT-scan

revealed signicant shrinkage of the bulky tumor mass. e radiological

re-assessment ve months aer initiation demonstrated further decreas-

ing tumor size. e clinical performance status improved signicantly and

therapy with pembrolizumab is still ongoing.

Conclusions: ICI are able to provide durable tumor response in pretreat-

ed MSI-high mCRC patients. erefore, we emphasize the importance

of testing for MSI. Further clinical studies are needed in order to verify

ecacy and safety of ICI in mCRC patients and to identify those patients

with MSI-high mCRC that do not benet from ICI therapy.

Disclosure Statement: No conict of interest.

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349

Age-Specic Sequence of Colorectal Cancer Screening oers

in Germany: Model-Based Critical Evaluation

Thomas Heisser 1, 2; Korbinian Weigl 1, 3; Michael Homeister 1;

Hermann Brenner 1, 3, 4

1Clinical Epidemiology and Aging Research, German Cancer Research Center

(DKFZ), Heidelberg, Deutschland

2Medical Faculty, University of Heidelberg, Heidelberg, Deutschland

3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and

National Center for Tumor Diseases (NCT), Heidelberg, Deutschland

Purpose: e current oer of the organized screening program for col-

orectal cancer (CRC) in Germany implies that both sexes can have up to

ve annual fecal immunochemical tests (FITs) between ages 50-54, fol-

lowed by a rst screening colonoscopy at age 55 in case all of these FITs

were negative. We sought to assess the performance of this oer.

Methods: Using a multistate Markov model, we quantied the expected

prevalences of neoplasms in a population perfectly adhering to annual FIT

screening between ages 50-54 to assess the detection rates and numbers

needed to scope one case of (non-)advanced adenoma or cancer (NNS) of

colonoscopic screening at age 55. We additionally modelled the diagnostic

performance of such consecutive annual FIT testing.

Results: In subjects with ve consecutive negative FITs, expected colo-

noscopy detection rates (NNS) of any neoplasm, any advanced neoplasm

and cancer at age 55 are 10% (10), 1.9% (52) and 0.05% (2,089), respec-

tively, in women, and 17% (6), 3.5% (28) and 0.09% (1,058), respectively,

in men. Positive predictive values (PPVs) for advanced neoplasms drop

from 14.0% and 22.4% in year 1 to 8.4% and 13.9% in year 5, and PPVs

for cancers from 2.4% and 3.9% to 0.6% and 1.0%, for women and men,

respectively.

Conclusions: Our ndings suggest that the current screening oer in

Germany of ve consecutive FITs from ages 50-54, followed by screening

colonoscopy at age 55 aer ve negative FITs, may be highly inecient as

perfect adherence would go along with very low PPVs of repeat annual

FITs and very high NNS of screening colonoscopy at age 55. e design of

the FIT screening oer should be re-evaluated.

Disclosure Statement: e authors declare that they have no conict of interest.

352

Outcomes at Follow-Up of a Negative Colonoscopy

in the Average-Risk Population: a Systematic Review

and Meta-Analysis

Thomas Heisser 1, 2; Le Peng 1, 2; Korbinian Weigl 1, 3; Michael Homeister 1;

Hermann Brenner 1, 3, 4

1Clinical Epidemiology and Aging Research, German Cancer Research Center

(DKFZ), Heidelberg, Deutschland

2Medical Faculty, University of Heidelberg, Heidelberg, Deutschland

3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

4Division of Preventive Oncology, German Cancer Research Center (DKFZ) and

National Center for Tumor Diseases (NCT), Heidelberg, Deutschland

Purpose: To review and summarize the evidence on the prevalence of col-

orectal adenomas and cancers at a follow-up screening colonoscopy aer

negative index colonoscopy, stratied by interval between examinations

and by sex.

Methods: We systematically searched the electronic databases of PubMed,

Web of Science and EMBASE and performed meta-analyses of all avail-

able studies. Published studies were eligible for inclusion if they assessed

the outcome of a follow-up colonoscopy in subjects at average risk for

CRC with a negative previous colonoscopy (no adenomas).

Results: 28 studies were identied, including 22 cohort studies, 5

cross-sectional studies and 1 case-control study. Findings for an interval

between colonoscopies of one to ve, ve to ten, and more than ten years

were reported by 17, 16 and 3 studies, respectively. Summary estimates

(95% condence intervals) of rates of any neoplasms were 20.7% (15.8%

to 25.5%), 23.0% (18.0% to 28.0%) and 21.9% (14.9% to 29.0%) for one to

ve, ve to ten, and more than ten years between colonoscopies. Corre-

sponding summary estimates of rates of advanced neoplasms were 2.8%

(2.0% to 3.7%), 3.2% (2.2% to 4.1%) and 7.0% (5.3% to 8.7%). Seven stud-

ies also reported ndings stratied by sex. Summary estimates stratied by

interval and sex were consistently higher for men as compared to women.

Conclusions: Although detection of any neoplasms was observed in >20%

of subjects within ve years of a negative screening colonoscopy, detection

of advanced neoplasms within ten years was rare. Our ndings suggest

that ten-year colonoscopy screening intervals aer negative colonoscopy

(as currently recommended) may be adequate, but more studies are need-

ed to strengthen the empirical basis for pertinent recommendations and

to investigate even longer intervals.

Disclosure Statement: e authors declare that they have no conict of interest.

377

Long Term Survival of Patients with Stage IV Rectal

Cancer - Due to Targeting the Tumor Associated

Inammatory Process?

Bernhard Koch 1; Lutz Uacker 1; Ayoub Abdu 1; Andrea Tannapfel 2

1Datteln, St. Vincenz-Krankenhaus, Datteln, Deutschland

2Bochum, Institut für Pathologie, Bochum, Deutschland

Purpose: e median overall survival time of patients with stage IV rectal

cancer is less than 3 years. We present cases of 2 patients with rectal cancer

who survived initial diagnosis of metastasis for 9 and more than 11 years,

respectively. We speculate on the possible reason for this favorable course.

Case reports: Patient 1 was a 66 year old lady who was operated because

of rectal cancer UICC stage I. 18 months later she developed skin and

hepatic metastasis, received resection and was treated with regimens

containing FOLFOX, bevacizumab, FOLFIRI, cetuximab, irinotecan,

CAPOX, panitumumab, mitomycin, and aibercept. She died 9 years aer

diagnosis of metastasis. Patient 2, aged 61 years, initially presented with

metastasis to the peritoneum and later on to abdominal wall and lung.

During the course she was treated with regimens containing bevacizum-

ab, FOLFIRI, capecitabine, FOLFOX, cetucimab, and ramucirumab. She

received several tumor resections and irradiation. Currently she is living

more than 11 years aer diagnosis of metastasis.

Discussion: A survival of more than 9 years in stage IV rectal cancer is re-

markable. Based upon animal studies a strategy combining antiangiogenic

therapy with long term applcation of capecitabine has been proposed (1).

In the human situation single cases of the benecial eects of long term

metronomic capecitabine have been reported. e patients described

here received a long term therapy with regimens containing anti-VEGF,

or VEGFR-2 directed modalities, and drugs targeting endothelium and

tumor supporting myeloid cells.

Conclusions: Besides targeting tumor cells itself the long lasting inhib-

tion of angiogenesis proves to be an important factor to achieve long term

disease stabilisation.

e spectrum of drugs targeting cells of the intra- and peritumoral in-

ammatory rection is wide and aggravates the interpretion of single fac-

tors responsible for a benecal course.

Report more of those cases with a noticeable survival time.

Reference:

1. Zhang Y et al, PNAS 2017, PMID: 28607065

Disclosure Statement: e authors declare no conict of interest.

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426

Real-World Testing Patterns for Braf-Mutations and Treatment

of Patients with Braf-Mutated Metastatic Colorectal Cancer:

Results from The German Tumor Registry Colorectal Cancer

(TKK Registry)

Mark-Oliver Zahn 1; Steen Dörfel 2; Holger Schulz 3; Thomas Wolf 4;

Ursula Vehling-Kaiser 5; Susanne Tech 6; Martina Jänicke 6; Natalie Wetzel 6;

Norbert Marschner 7

1Studienzentrum MVZ Onkologische Kooperation Harz, Goslar, Deutschland

2Onkozentrum Dresden/ Freiberg, Dresden, Deutschland

3Praxis Internistischer Onkologie und Hämatologie (PIOH), Frechen,

Deutschland

4BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland

5Hämatologisch-onkologische Tagesklinik, Landshut, Deutschland

6iOMEDICO, Freiburg, Deutschland

7Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland

Purpose: BRAF-mutations have been reported in approximately 8-12 %

of patients (pts) with metastatic colorectal cancer (mCRC), with V600E

being the most common mutation. Despite major improvements in sur-

vival for mCRC overall, BRAF-mutant mCRC typically appears refractory

to standard chemotherapy for mCRC and is associated with a poor prog-

nosis with a median overall survival of less than 12 months. Real-world

data on the identication and treatment of this high medical need popu-

lation are scarce.

Methods: Since 2006, the Tumor Registry Colorectal Cancer (TKK) pro-

spectively documents treatment of CRC pts in clinical routine in Germa-

ny. Pts are treated according to physician’s choice. Data on pts and tumor

characteristics, all systemic treatments including rst-line and subsequent

line treatments, outcome and quality of life are collected. In addition,

since 2018 data on BRAF testing are documented. Here, we analyzed

BRAF-mutation testing patterns and treatment of pts with BRAF-mutant

mCRC. Analyses were ongoing at the time of submission.

Results: Until data base cut 31.03.2019, 4334 pts with mCRC had been

enrolled at initiation of palliative rst-line treatment, 474 pts from 91 sites

since data on BRAF testing is collected. Of those, 65% (310 pts) were test-

ed for BRAF mutation with positive results documented in 48 patients

(10% of all, 15% of tested pts). Results will be presented regarding charac-

teristics (age, gender, ECOG performance status, tumor localization, RAS

status, MSI status, time between primary diagnosis until start of rst-line

therapy) and treatment patterns (1st, 2nd, 3rd line) of pts with and without

BRAFmutation testing and with and without BRAF mutation.

Conclusions: is analysis of the TKK data provides important insights

into the testing and treatment patterns of patients with BRAF-mutant

mCRC treated in clinical routine in Germany.

Disclosure Statement: None of the authors has declared a conict of interest

regarding the subject of this work.

466

Perioperative Therapy of Locally Advanced Adenocarcinoma

in the Upper Third of The Rectum - Long-Term Results

of Dierent Therapeutic Approaches

Johannes Reber 1; Michael Gerken 1; Teresa Draeger 2; Sophia Scharl 3;

Vinzenz Völkel 4; Alois Fürst 4; Monika Klinkhammer-Schalke 1

1Tumor Center, Institute for Quality Management and Health Services Research,

University of Regensburg, Regensburg, Deutschland

2Caritas Krankenhaus St. Josef Regensburg, Klinik für Innere Medizin,

Regensburg, Deutschland

3Department of Radiation Oncology, Klinikum rechts der Isar, Technische

Universität München (TUM), München, Deutschland

4Caritas Krankenhaus St. Josef Regensburg, Klinik für Allgemein-, Viszeral-,

Thoraxchirurgie und Adipositasmedizin, Regensburg, Deutschland

Purpose: e German S3-guideline’s recommendations for the perioper-

ative treatment of stage II and III rectal cancer in the upper third of the

rectum have recently changed. Between 2008 and 2017 it was up to the

treating physician whether to follow the guideline’s recommendations on

rectum- or on colon carcinoma; nowadays, there is a clear statement in

favor of the colon line of treatment.

Methods: Based on a cohort of 5,312 patients diagnosed with stage II/

III upper third rectum cancer between 2000 and 2016, gathered by 30

clinical cancer registries in Germany, we performed a comparison of 462

cases of neoadjuvant radiochemotherapy and adjuvant chemotherapy

combined and 1,049 cases of adjuvant chemotherapy only, with regard to

the outcome quality of the dierent perioperative therapeutic approaches

for locally advanced upper third rectum cancer in clinical practice. Us-

ing Kaplan-Meier, uni- and multivariable Cox-regression analyses, over-

all survival, disease-free survival, local and distant recurrence rates were

calculated.

Results: Patients in UICC stage II/III who received neoadjuvant

radiochemotherapy and adjuvant chemotherapy combined had, according

to the multivariable analyses, no signicant dierences concerning

overall survival, disease-free survival or local and distant metastases

rates as compared to patients receiving adjuvant chemotherapy only.

e corresponding cumulative 5-year local recurrence rates were 4,1%

and 5,6% respectively. In contrast, patients with UICC stage III and an

elevated risk prole (subgroup analyses for: stage III T4 and stage III N2)

showed a signicantly worse disease free survival when they had obtained

adjuvant chemotherapy only (HR=3,225, 95%-CI=1,140-9,123, p=0,027 /

HR=2,352, 95%-KI=1,153-4,798, p=0,019).

Conclusions: e recommendations of the German S3-guideline of 2017

to refrain from neoadjuvant radiation therapy in low-risk patients with

a tumor in the upper third of the rectum are supported by the results of

this study.

Disclosure Statement: e authors declare no conict of interest.

512

The Inuence of Diabetes Mellitus (DM) on Morbidity and

Mortality as well as Oncological Outcome in Colon Cancer (CA)

Surgery – Interims Analysis

Romy Kreyer 1; Ronny Otto 2; Stefanie Wol 1; Ingo Gastinger 2;

Hans Lippert 2; Henry Ptok 1; Roland S. Croner 1; Frank Meyer 1

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Purpose: To investigate the inuence of DM as well as the factors associ-

ated with this metabolic disease, on early postop. & long-term oncological

outcomes following colon Ca surgery.

Methods: Patients with colon Ca -/+ DM were registered in this prospec-

tive multi-center observational study. Early postop. & long-term onco-

logical outcome was specically characterized by morbidity/in-hospital

mortality & 5-yr-overall survival (5-yr-OS), 5-yr-disease-free survival

(5-yr-DFS) & 5-yr-local recurrence rate (5-yr-LRR), resp.

Results: In total, 9167 patients were enrolled who were subdivided as fol-

lows: 20.5% w/ DM (insulin-dependent, 37.8%) & 79.5% w/o DM (age

range of +/- DM patients, 34-97 vs. 18-98 yr; sex ratio [m/f], 52.9/47.1%

vs. 56,2/43,8%). e initially higher progression rates of tumor (Tu) dis-

ease (P=0.018) as well as the more advanced Tu stages according to the

UICC classication was found in DM patients (P=0.293). Furthermore,

DM patients showed signicantly worse ASA scoring (P<0.001). With

a total morbidity of 35.8%, DM patients had signicantly more general

postop. complications (P<0.001). However, the slightly higher rate of spe-

cial postop. complications in DM patients was not signicant (P=0.224).

With a total in-hospital mortality of 4.2%, DM patients showed a signi-

cantly higher rate (P<0.005). DM patients had a signicantly lower 5-yr-

OS (DM, 49.8% vs. non-DM 59.7%; P<0.001). A clearly worse 5-yr-DFS

was also found in the DM category (DM, 57.7% vs. non-DM, 67.6%,

P<0.001). e surprisingly lower 5-yr-LRR of DM vs. non-DM patients

was not signicant (2.4% vs. 2.8%, P=0.664).

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2018

Index

2018

Conclusions: e highest postop. complication rates as well as the worst

5-yr-OS and the lowest 5-yr-DFS were found in the DM patients.

Disclosure Statement: Nothing to be disclosed.

515

Body Mass Index (BMI) Dependent Outcome in Colon

Cancer(CA) Surgery – Interims Results of a Prospective

Multi-Center Observational Study

Romy Kreyer 1; Ronny Otto 2; Hans Lippert 2; Ingo Gastinger 2; Henry Ptok 1;

Roland S. Croner 1; Frank Meyer 1

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Purpose: To verify the impact of BMI onto immediate post-op. & long-

term oncological outcomes following colon Ca surgery.

Methods: Patients (nTotal=8,574; mean age, 71 [range, 18-98] yrs; sex ratio,

m:f=53.7:46.3%) were classied according to WHO denitions for BMI

into under-/normal-/overweight & obese (<18.5/18.5-24.9/25-29.9/>30

kg/m2, resp.).

Early postop. outcome comprised morbidity & hospital mortality.

Long-term oncological outcome was specically characterized by

5-yr-overall survival (5-yr-OS), 5-yr-disease-free survival (5-yr-DFS) &

5-yr-local recurrence rate (5-yr-LRR).

Results: e relative portions for the BMI categories were as follows:

Under-, 2.1%; normal-, 36.5%; overweight, 40.3% & obese, 21.2%. e

highest progression of the Tu disease was found in the underweight pa-

tients. More advanced Tu stages (according to UICC classication) were

detected in the normal weight group compared to overweight & obese

patients (P<0.001 each). In addition, both underweight & obese patients

showed worse ASA scoring (P<0.001). With a total morbidity of 35%,

obese patients suered most from surgical complications (P<0.001) vs.

underweight category was associated with the highest rate of general

complications aer surgical intervention (P=0.183). e overall in-hos-

pital mortality was 3.7%. Obese subjects had better 5-yr-OS (63.1%) than

normal weight individuals (54.4%; P<0.001). In addition, overweight cas-

es were not dierent compared to obesity (P=0.205). e lowest 5-yr-OS

rates were found in the underweight group of patients (38.9%; P<0.001

- overall 5-yr-OS, 58.8%).With the lowest proportion of local recurrences

(5-yr-LRR, 1.4%), only the obesity category had a signicant inuence on

5-yr-LRR (P<0.016; LRR in total, 2.88%). Despite the higher 5-yr-LRR in

the underweight cases, it was not signicantly dierent (P>0.264).

Conclusions: Results are similar to previously obtained rectal Ca data on

long-term outcome emphasizing the obesity paradox.

Disclosure Statement: Nothing to be disclosed.

516

Multicenter Study Results on Colon Cancer Conducted

by a Single Research Group – an Overview

Frank Meyer 1; Henry Ptok 1; Ralf Steinert 2; Ronny Otto 3; Ingo Gastinger 3;

Hans Lippert 3

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Dept. of General and Abdominal Surgery, St Josef Hospital at Salzkotten,

Salzkotten, Deutschland

3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Purpose: To summarize results on the surgical management of colon

cancer(Ca), its quality assurance & their consequences for daily surgical

practice.

Methods: Prospective multicenter observational study data on diagnos-

tic, treatment & outcome of patients with colon Ca over a dened study

period.

Results (selective):

1) Case load in general does not provide necessarily a signicant

impact onto the outcome.

2) Age can be considered a risk factor, however, it can not be

considered a contraindication for surgcial treatment of colon Ca.

3) Hartmann’s procedure is still indicated in high-risk patients &

emergency cases to reduce morbidity & mortality.

4) Hospital volume does not provide a signicant impact onto the

early postop. outcome.

5) Implantation of self-expanding stents (SEMS) can be considered

an ecient measure in endoscopic palliation of the malignant

colonic stenosis – it reduces postop. complications in bridging of

stenosing tumor growth of colon Ca until surgical intervention.

6) Laparoscopic approach in resection of colon Ca is reasonable

in a well dened portion of patients; it should be performed

by experienced surgeons since conversion to open surgery is

associated with a signicant increase of morbidity, mortality &

hospital stay.

7) Anastomotic insuciency in colon resection is a rare but severe

complication, which is associated with specic risk factors.

Conclusions: e aquisition of such data can provide important hints &

knowledge for future care.

Disclosure Statement: Nothings has to be disclosed.

517

Quality Assurance in Rectal Cancer - Multicenter Study Results

Obtained By One Research Group

Frank Meyer 1; Ralf Steinert 2; Henry Ptok 1; Ronny Otto 3; Hans Lippert 3;

Ingo Gastinger 3

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Dept. of General and Abdominal Surgery, St Josef Hospital at Salzkotten,

Salzkotten, Deutschland

3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Purpose: To analyze data on diagnostic & treatment prole, outcome as

well as quallity assurance of surgical care in the management of rectal can-

cer(Ca).

Methods: Prospective multicenter observational study (design) in pa-

tients with rectal Ca over a dened study period.

Results:

- Hospital volume did not have a signicant impact onto the oncosur-

gical long-term outcome.

- Neoadjuvant radiochemotherapy did not increase the risk of a

postoperative anastomotic insuciency or dysfunction of the

urinary bladder aer sphincter-preserving rectal resection with

curative intention.

- Creation of a protective enterostoma did not reduce the frequency of

a postop. anastomotic insuciency but it lowered the frequency of

following surgical or interventional consequences.

- Quality of TME depends on patient- & treatment-associated factors.

- Patient’s age is a risk factor but it can not be considered a general

contraindication for resection of rectal Ca.

- Oncological outcome aer laparoscopic rectum resection is compa-

rable with that aer open resection (worsening aer conversion).

- Limited resection of pT1-low-risk carcinoma may provide an accept-

able oncosurgcial outcome.

- Rate of abdominoperineal rectum exstirpation (APR) has been re-

duced in routine surgical care down to approximately 20%.

Conclusions: e results i) reect real situation in abdominal surgery in

Germany, ii) have inuenced disease-specic clincial management, and

iii) may dene novel subjects of up-coming studies.

Disclosure Statement: Nothing to be diosclosed.

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2018

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2018

543

Colorectal Cancer Screening with Fecal Immunochemical

Tests – The Impact of Anatomical, Morphological and

Histopathological Adenoma Characteristics on Test

Sensitivity: Systematic Review and Meta-Analysis

Jovan Todorovic 1; Beate Jahn 1, 2; Marija Mladenovic 1; Gaby Sroczynski 1;

Ursula Rochau 1; Sibylle Puntscher 1; Jùlia Santamaria 1; Valentino Allende 1;

Slavica Stojnev 3; Uwe Siebert 1, 2, 4, 5

1Institute of Public Health, Medical Decision Making and Health Technology

Assessment, Department of Public Health, Health Services Research and Health

Technology Assessment, UMIT – Private University for Health Sciences, Medical

Informatics and Technology, Hall in Tirol, Österreich

2Division of Health Technology Assessment and Bioinformatics, ONCOTYROL –

Center for Personalized Cancer Medicine, Innsbruck, Österreich

3Department of Pathology, Faculty of Medicine, University of Nis, Niš, Serbia

4Center for Health Decision Science, Department of Health Policy and

Management, Harvard Chan School of Public Health, Boston, MA, USA

5Institute for Technology Assessment and Department of Radiology,

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Purpose: Fecal immunochemical tests (FIT) are recommended for col-

orectal cancer (CRC) screening. Dierent adenoma characteristics can af-

fect FIT sensitivity. We aimed to systematically investigate adenoma char-

acteristics inuencing FIT sensitivity and leading to false-negative results.

Methods: Literature search was conducted in MEDLINE, Cochrane Li-

brary and EMBASE databases. Included studies had to provide quantita-

tive information on FIT sensitivity with regard to dierent specic adeno-

ma characteristics. We limited our search to articles published 2010-2019

in English language. Evidence tables were used to systematically combine

study characteristics. e dierences between sensitivity of distal and

proximal adenomas were pooled using a xed eects meta-analysis model

and 95% condence intervals (CI) were calculated.

Results: 11 studies were included in our review. Study designs varied with

8 prospective and 3 retrospective studies. Identied characteristics leading

to low FIT sensitivity are proximal localization, non-polypoid morphol-

ogy and serrated type. e pooled absolute dierence in FIT sensitivity

between proximal and distal adenomas was 15% (95% CI: 11%-19%). FIT

sensitivity was signicantly lower for at as compared to non-at adeno-

mas (11%). e largest statistically signicant dierence between sessile

serrated (SSA/P) and conventional advanced adenoma was 20%. FIT re-

sults in high proportion of false-negative results (16%) for patients with

proximal and small (≥10 mm) or at adenomas.

Conclusions: Our ndings suggest that localization in the proximal co-

lon, at adenomas and SSA/Ps are the most unfavorable for detection in

early stages when the curative treatment could prevent CRC development.

Imperiale TF, et al. 2019.

Niedemaier T, et al. 2018.

Disclosure Statement: No conict of interest.

569

Integrated Biobanking and Tumor Model Establishment

of Human Colorectal Carcinoma Provides Excellent Tools

for Modern Precision Medicine

Christina Mullins 2; Bianca Micheel 1; Stephanie Matschos 1;

Matthias Leuchter 1; Florian Bürtin 1; Maja Hühns 3; Ernst Klar 1;

Friedrich Prall 3; Michael Linnebacher 1

1Chirurgie, Universitätsmedizin Rostock, Rostock, Deutschland

2Thoraxchirurgie, Universitätsmedizin Rostock, Rostock, Deutschland

3Pathologie, Universitätsmedizin Rostock, Rostock, Deutschland

Purpose: Over the time period from 2006 to 2017, consecutive patients

operated on at the University Medical Center Rostock participated in this

comprehensive biobanking and tumor-modelling approach: the HROC

collection. Samples were collected using strict SOP including blood (se-

rum und lymphocytes), tumor tissue (vital and snap frozen) as well as ad-

jacent normal epithelium. Patient and tumor data including classication,

molecular type, clinical outcome and results of model establishment are

the essential pillars.

Methods: Overall 149 patient-derived xenogras, 34 primary and 35 sec-

ondary cell lines were successfully established and encompass all colorec-

tal carcinoma anatomic sites, grading and staging types and molecular

classes. e HROC collection represents one of the largest model assort-

ments from consecutive clinical CRC cases worldwide.

Results: Statistical analysis identied a variety of clinicopathological and

molecular factors associated with model success in univariate analysis;

several of them not identied before: localization, mutational status of

K-Ras and B-Raf, MSI-status as well as grading and staging parameters.

Surprisingly, in multivariate analysis model success solely correlated pos-

itively with the nodal status N1 and mutations in the genes K-Ras and

B-Raf. ese results imply that generating CRC tumor models on the in-

dividual patient level is worth considering especially for advanced tumor

cases with a dismal prognosis.

Conclusions: In sum, this study succeeded in generating CRC in vitro

and in vivo models from all subtypes of CRC with the exception of FAP.

To the best of our knowledge, the HROC collection represents the largest

single-center integrated biobanking activity of CRC-patient biomateri-

al plus individual-patient-derived in vitro and matching in vivo models

worldwide. Several clinical and molecular factors signicantly inuencing

success of model generation were identied – many for the rst time. All

models are available upon reasonable request.

Disclosure Statement: none to declare

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2018

Index

2018

608

Beacon Crc: a Randomized, Phase 3 Study of Encorafenib

(ENCO) and Cetuximab (CETUX) with or without Binimetinib

(BiNI) vs. Choice of Either Irinotecan or Folri Plus Cetux in

BRAF V600E–Mutant Metastatic Colorectal Cancer (mCRC)

Arndt Vogel 1; Susanna Hegewisch-Becker 2; Gerald Prager 3;

Gunnar Folprecht 4; Michael Stahl 5; Scott Kopetz 6; Axel Grothey 7;

Eric van Cutsem 8; Rona Yaeger 9; Harpreet Wasan 10; Takayuki Yoshino 11;

Jayesh Desai 12; Fortunato Ciardello 13; Ashwin Gollerkeri 14; Kati Maharry 14;

Fotios Loupakis 15; Hong Y 16; Neeltje Steeghs 17; Tormod Kyrre Guren 18;

Hendrik-Tobias Arkenau 19; Pilar García-Alfons 20; Victor Sandor 14;

Janna Christy-Bittel 21; Lisa Anderson 14; Josep Tabernero 22

1Gastroenterology, Hepatology and Endocrinology, Hannover Medical School,

Hannover, Deutschland

2HOPE-Practice for Oncology, Hamburg, Deutschland

3Department of Medicine, Medical University of Vienna, Vienna, Österreich

4University Clinic Dresden, Oncology Department, Dresden, Deutschland

5Department of Medical Oncology and Hematology, Evang. Kliniken Essen-

Mitte, Essen, Deutschland

6UT MD Anderson Cancer Center, Houston, TX, United States

7Mayo Clinic, Rochester, Minnesota, United States

8UZ Leuven-Campus Gasthuisberg, Leuven, Belgien

9Memorial Sloan-Kettering Cancer Center, New York, NY, United States

10Hammersmith Hospital, Department of Cancer Medicine, London, United

Kingdom

11Department of Gastroenterology and Gastrointestinal Oncology, National

Cancer Hospital East, Kashiwa, Japan

12Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Walter and

Aliza Hall Institute, Parkville, VIC, Australien

13Università degli Studi della Campania L., Dipartimento di Medicina di

Precisione, Napoli, Italien

14Array BioPharma Inc, Boulder, CO, United States

15Medical Oncology Unit 1, Clinical and Experimental Oncology Department,

Veneto Institute of Oncology IOV-IRCCS, Padua, Italien

16Asan Medical Center, Seoul KR, Seoul, Südkorea

17Netherlands Cancer Institute, Amsterdam, Niederlande

18Oslo University Hospital, Oslo, Norwegen

19Sarah Cannon Research Institute, HCA Healthcare, London, United Kingdom

20Medical Oncology Department. Hospital General Universitario Gregorio

Marañón, Madrid, Spanien

21Array BioPharma Inc, Cambridge, MA, United States

22Vall d’Hebron University Hospital, Barcelona, Spanien

Purpose: BRAF V600E mutations are identied in up to 15% of mCRC

patients (pts) and confer a poor prognosis. Objective response rates

(ORR) to chemotherapy in ≥ 2 line are generally less than 10%, with me-

dian progression-free survival (PFS) and overall survival (OS) of approx-

imately 2 and 4-6 months, respectively. A 30-patient safety lead-in with

ENCO+BINI+CETUX showed acceptable safety and encouraging activity

in these pts.

Methods: e BEACON CRC Study (NCT02928224) was a multicenter,

randomized, open-label, phase 3 study to evaluate ENCO+CETUX with/

without BINI (triplet or doublet) vs. choice of irinotecan or FOLFIRI +

CETUX (control) in pts with BRAF V600E‒mutant mCRC who had pro-

gressed aer 1 or 2 prior palliative regimens. e primary endpoints were

OS and ORR (by blinded central review) comparing triplet to control arm;

secondary end points included OS for the doublet arm as well as PFS and

safety.

Results: 665 pts were randomly assigned to the triplet (n = 224), doublet

(n = 220), or control arm (n = 221). Median OS was 9.0 months (95% CI,

8.0-11.4) for the triplet and 5.4 months (95% CI, 4.8-6.6) for the control

regimen (HR, 0.52; 95% CI, 0.39-0.70, p < .0001). Conrmed ORR of the

triplet was 26% and 2% for the control (p < .0001). Median OS for the

doublet combination was 8.4 months (95% CI, 7.5-11.0) (HR vs. control,

0.60; 95% CI, 0.45-0.79; P = .0003). Adverse events were as anticipated

based on prior trials with each combination. Grade 3 or 4 adverse events

were seen in 58%, 50% and 61% of pts in the triplet, doublet and control

arm, respectively.

Conclusions: ENCO+BINI+CETUX improved OS and ORR in pts with

BRAF V600E-mutant mCRC when compared with current standard of

care chemotherapy and had a safety prole consistent with the known

safety prole of each agent. is targeted therapy regimen should be a

new standard of care for this patient population.

e study was published at ESMO World GI congress 2019.

Conicts of Interest: AV: honoraria from Pierre Fabre.; GP: speaker, advisory

board member, other type of consultant: Celgene, Bayer, Roche, Shire, Halozyme,

Lilly, BMS, Pierre Fabre, Amgen, Servier, MSD, Merck, Taiho; GF: honoraria from

Merck, Roche, Sano-Aventis, Lilly, Bayer, Servier, Mundipharma, BMS, MSD;

Research funding: Merck; SK: Stock and Other Ownership Interests: Molecular-

Match, Navire Consulting or Advisory Role: Roche, Genentech, EMD Serono,

Merck, Karyopharm erapeutics, Amal erapeutics, Navire Pharma, Sympho-

gen, Holy Stone, Biocartis, Amal erapeutics, Amgen, Novartis, Eli Lilly, Boeh-

ringer Ingelheim; AG: Honoraria: Elsevier, Aptitude Health Consulting or Adviso-

ry Role: Genentech (Inst), Bayer (Inst), Bristol-Myers Squibb (Inst), Eli Lilly (Inst),

Boston Biomedical (Inst), Amgen (Inst), Array BioPharma (Inst), Guardant Health

(Inst), Daiichi Sankyo (Inst), Research Funding: Genentech (Inst), Bayer (Inst),

Pzer (Inst), Eisai (Inst), Eli Lilly (Inst), Boston Biomedical (Inst), Daiichi Sankyo

(Inst), Array BioPharma (Inst); Travel, Accommodations, Expenses: Genentech,

Bayer, Bristol-Myers Squibb, Boston Biomedical, Amgen, Boehringer Ingelheim,

Merck Sharp & Dohme; EVC: Consulting or Advisory Role: Bayer, Eli Lilly, Roche,

Servier, Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, Merck KGaA,

Novartis, AstraZeneca; Research Funding: Amgen (Inst), Bayer (Inst), Boehringer

Ingelheim (Inst), Eli Lilly (Inst), Novartis (Inst), Roche (Inst), Celgene (Inst),

Ipsen (Inst), Merck (Inst), Merck KGaA (Inst), Servier (Inst), Bristol-Myers Squibb

(Inst); RY: Research Funding: Array BioPharma, GlaxoSmithKline, Novartis;

Travel, Accommodations, Expenses: Array BioPharma; Speakers’ Bureau: Sysmex;

Research Funding: Symphogen; Patents, Royalties, Other Intellectual Property:

Patent licensed by Biocartis (Inst); HW: Honoraria: Merck KGaA, Celgene, Sirtex

Medical, Servier, Array BioPharma, Shire, Genentech, ERYTECH Pharma; Con-

sulting or Advisory Role: Roche Pharma AG, SITEX Medical, ERYTECH Pharma,

Shire, Incyte; Speakers’ Bureau: Sirtex Medical, Celgene, Merck KGaA, Servier;

Research Funding: Sirtex Medical (Inst), Merck KGaA (Inst), Pzer (Inst), Merck

Sharp & Dohme (Inst); TY: Research Funding: Chugai Pharma (Inst), Sano (Inst),

Sumitomo Dainippon (Inst), GlaxoSmithKline (Inst); JD: Consulting or Advisory

Role: Bionomics, Eli Lilly, Eisai, BeiGene, Ignyta (Inst); Research Funding: Roche

(Inst), GlaxoSmithKline (Inst), Novartis (Inst), Bionomics (Inst), MedImmune

(Inst), BeiGene (Inst), Eli Lilly (Inst), Bristol-Myers Squibb (Inst); FC: Consult-

ing or Advisory Role: Genentech, Merck KGaA, Bayer, Amgen, Pzer; Research

Funding: Merck KGaA (Inst), Genentech (Inst), Servier (Inst), Symphogen (Inst),

Amgen (Inst), Bayer (Inst), Merck Sharp & Dohme (Inst), Bristol-Myers Squibb

(Inst), Ipsen (Inst); AG: Employment: Array BioPharma, Alnylam (I), Bluebird Bio

(I); Stock and Other Ownership Interests: Array BioPharma, Alnylam (I); Hon-

oraria: Bluebird Bio (I); Patents, Royalties, Other Intellectual Property: Receives

royalties from Yale University on an antibody used in nephrology basic research

(I); KM: Employment: Array BioPharma; Stock and Other Ownership Interests:

Array BioPharma; Travel, Accommodations, Expenses: Array BioPharma; NS:

Research funding (inst): ompany: AstraZeneca/MedImmune, Bayer, Bristol-Myers

Squibb, Novartis, GlaxoSmithKline, Pzer, Roche, Genentech/Roche, Boehringer

Ingelheim, Blueprint Medicines, AB Science, Deciphera, Blueprint Medicines,

Genentech, Merck Sharp & Dohme, Amgen, Merus, Lilly, Incyte; VS: Employment:

Array BioPharma; Leadership: Array BioPharma; Stock and Other Ownership

Interests: Array BioPharma; JCB: Employment: Array Biopharma; Stock and Other

Ownership Interests: Array Biopharma, Gilead Sciences; LA: Array employee;

Employment: Array BioPharma; Stock and Other Ownership Interests: Array

BioPharma; Travel, Accommodations, Expenses: Array BioPharma; JT: Consulting

or Advisory Role: Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Merck Serono,

Novartis, Sano, Taiho Pharmaceutical, Merrimack, Peptomyc, Rafael Pharmaceu-

ticals, Symphogen, Chugai Pharma, Ipsen, Merus, Pzer, Seattle Genetics, Array

BioPharma, AstraZeneca, BeiGene, Genentech, Genmab, Halozyme, Imugene

Limited, Inection Biosciences Limited, Kura, Menarini, Molecular Partners,

Pharmacyclics, ProteoDesign SL, Roche, Seattle Genetics, Servier, VCN Bioscienc-

es, Biocartis, Foundation Medicine, HalioDX SAS, Roche Diagnostics; FT, YH, TG,

TA, PGA have nothing to dislose.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts56

Inhalt

2018

Index

2018

627

Are Visceral Obesity and Sarcopenia Postoperative Risk

Factors for Patients Undergoing Hepatic Resections for

Synchronous Colorectal Liver Metastases?

Mira Runkel 1; Thierno Diallo 2; Fabian Bamberg 2; Stefan Fichtner-Feigl 1;

Sven A. Lang 1

1Universitätsklinikum Freiburg, Klinik für Allgemein-und Viszeralchirurgie ,

Freiburg im Breisgau, Deutschland

2Universitätsklinikum Freiburg, Klinik für Radiologie , Freiburg im Breisgau,

Deutschland

Purpose: e impact of body fat composition on surgical outcomes is

controversial. is study examined whether sarcopenia or visceral obesi-

ty were risk factors aer hepatic resection of synchronous colorectal liver

metastases.

Methods: 94 consecutive patients with primary hepatic resections for syn-

chronous colorectal metastases were identied from a single cancer center

database between January 2013 and August 2018. Body fat distribution

and sarcopenia were retrospectively calculated from single-slice CT im-

ages at the level of L3.

Results: 63,8% (n=60) of patients had postoperative complications, where-

as only 18,1% (n=17) had major complications (Clavien-Dindo grade IIIb

and above). 36,2 % (n=34) of patients had sarcopenia and 70,2% (n=66)

were viscerally obese. Dierent denitions for visceral obesity included

visceral fat area (VFA) > 100cm², VFA >168cm² for men and >80 cm² for

women and visceral to subcutaneous fat ratio (V/S) >0,4. All denitions

of visceral obesity showed a signicant impact on postoperative compli-

cations (p=0,002, p=0,014, p=0,015, respectively). Higher grades of com-

plications were observed with viscerally obese patients (p=0,002). BMI

was not a predictor for postoperative outcomes (p=1,0). Sarcopenia was

not signicantly associated with postoperative complications (p=0,461),

however, it was shown to increase the length of hospital stay (p=0,028).

Neither sarcopenia nor visceral obesity had an impact on overall survival.

Conclusions: Visceral obesity but not sarcopenia correlates with short-

term postoperative outcomes aer hepatic resections and may thus serve

for better preoperative risk stratication.

Disclosure Statement: No Disclosures.

661

Beyond Proximal or Distal Location: Colonoscopy and

Reduction of Colorectal Cancer Risk By Molecular Subtypes

and Pathways

Michael Homeister 1; Hendrik Bläker 2; Lina Jansen 1; Elizabeth Alwers 1;

Efrat Amitay 1; Prudence Carr 1; Matthias Kloor 3; Esther Herpel 3;

Wilfried Roth 4; Jenny Chang-Claude 1; Hermann Brenner 1

1Klinische Epidemiologie und Alternsforschung, Deutsches

Krebsforschungszentrum, Heidelberg, Deutschland

2Institut für Pathologie, Universitätsmedizin Leipzig, Leipzig

3Institut für Pathologie, Universitätsklinik Heidelberg, Heidelberg

4Institut für Pathologie, Universitätsmedizin Mainz, Mainz

Purpose: In previous studies, the protective eect of colonoscopy was

generally stronger for distal than for proximal colorectal cancer (CRC)

(1,2). is study aimed to investigate whether the association of colonos-

copy and CRC risk varies according to major molecular pathological fea-

tures and pathways of CRC.

Methods: Population-based case-control study from Germany, including

2132 patients with a rst diagnosis of CRC and information on major

molecular tumor markers, and 2486 control participants without CRC.

Detailed participant characteristics were collected by standardized ques-

tionnaires and information on previous colonoscopy was derived from

medical records.

Results: Overall, we observed strong risk reduction of CRC aer colonos-

copy that was weaker for microsatellite instable (MSI) than for non-MSI

CRC (p for heterogeneity <0.0001), for CpG island methylator phenotype

(CIMP) high CRC than for CIMP low/negative CRC (p het=0.0011), for

BRAF-mutated than for BRAF non-mutated CRC (p het <0.0001), for

KRAS non-mutated than for KRAS-mutated CRC (p het=0.0415), and

for CRC classied into the sessile serrated pathway than for CRC of the

traditional pathway (p het=0.0009). Aer colonoscopy with detection of

adenomas, no risk reduction was found for sessile serrated pathway CRC.

Conclusions: Our study extends the molecular understanding of existing

dierences in risk reduction of proximal and distal CRC reported by pre-

vious studies, and may imply relevant information for improving strate-

gies for timely detection of relevant precursors.

References:

1. Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, et al. Long-

term colorectal-cancer incidence and mortality aer lower endoscopy. N Engl

J Med. 2013:1095-105.

2. Brenner H, Chang-Claude J, Jansen L, Knebel P, Stock C, Homeister M.

Reduced risk of colorectal cancer up to 10 years aer screening, surveillance,

or diagnostic colonoscopy. Gastroenterology. 2014:709-17.

Disclosure Statement: e authors declare that they have no conict of interest.

688

Utilization of Repeat Colonoscopies and Polypectomies

in Germany within 10 Years: a Claims Data Analysis Based

on More Than 2 Million Index Colonoscopies

Sarina Schwarz 1; Ulrike Haug 1, 2

1Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS, Bremen,

Deutschland

2Fachbereich 11 der Universität Bremen: Human- und

Gesundheitswissenschaften

Purpose: In Germany, >6 million colonoscopies are performed per year,

but longer-term follow-up data to monitor colonoscopy use at the indi-

vidual level are lacking. We aimed to explore the potential of German

claims data to describe the utilization and the diagnostic yield of repeat

colonoscopy.

Methods: We used the German Pharmacoepidemiological Research Da-

tabase (GePaRD), containing claims data with information on ~25 mil-

lion persons, to identify patients who underwent at least one colonoscopy

between 2006 and 2015. We only included persons with ≥2 years of con-

tinuous health insurance before the index colonoscopy. We excluded all

patients with a diagnosis code for colorectal cancer within 2 years before

index colonoscopy. We dened 3 sub-cohorts according to procedure/

diagnosis codes at index colonoscopy: Patients with a code for snare pol-

ypectomy (cohort 1), patients with no snare polypectomy but a diagnosis

code for polyps (cohort 2) and patients without such codes (cohort 3). We

described the sub-cohorts regarding utilization of and snare polypecto-

mies performed at repeat colonoscopy. All analyses were stratied by type

of index colonoscopy (diagnostic vs. screening).

Results: Overall, 2,520,445 persons with at least one colonoscopy were

included (cohort 1: 15%; cohort 2: 14%; cohort 3: 71%). e proportions

of persons entering cohorts with a screening colonoscopy were 47%, 39%

and 35%, respectively. Among these, the proportions with at least one re-

peat colonoscopy in cohort 1, 2 and 3 were 70%, 59% and 36%, and a

snare polypectomy at rst repeat colonoscopy was performed in 30%, 15%

and 10%, respectively. Among persons entering cohorts with a diagnostic

colonoscopy, the proportions with at least one repeat colonoscopy were

71%, 66% and 48%, and a snare polypectomy at rst repeat colonoscopy

was performed in 32%, 14% and 8% of these, respectively.

Conclusions: Claims data can provide useful information on utilization

of repeat colonoscopy in Germany and – although histological data are

lacking – provide an estimate on polyp detection.

Disclosure Statement: None.

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Inhalt

2018

Index

2018

704

KRAS Mutation Status Concordance Between the Primary Tumor

and the Corresponding Metastasis in Patients with Rectal Cancer

Peter Jo 1; Markus Bernhardt 1; Manuel Nietert 2; Alexander König 3;

Azadeh Azizian 1; Markus Schirmer 4; Marian Grade 1; Julia Kitz 5;

Michael Ghadimi 1; Philipp Ströbel 5; Hans-Ulrich Schildhaus 6;

Jochen Gaedcke 1

1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und

Kinderchirurgie, Göttingen, Deutschland

2Universitätsmedizin Göttingen, Abteilung für Medizinische Statistik

3Universitätsmedizin Göttingen, Klinik für Gastroenterologie und

gastrointestinale Onkologie

4Universitätsmedizin Göttingen, Abteilung für Strahlentherapie und

Strahlenonkologie

5Universitätsmedizin Göttingen, Abteilung für Pathologie

6Universitätsmedizin Duisburg-Essen, Abteilung für Pathologie

Purpose: KRAS is a negative predictive indicator for EGFR-treatment-

response in patients with colorectal cancer. We have shown KRAS mutation

status concordance in patients with locally advanced rectal cancer treated

preoperatively indicating no relevant heterogeneity within and between

multiple pre- and posttherapeutic samples of the primary tumor. e aim of

this study was to evaluate the heterogeneity of KRAS mutation status between

the primary tumor and the corresponding metastasis in the same collective

and to evaluate the ideal representative tissue for KRAS mutation testing.

Methods: KRAS mutation status analyses were performed in a previous

study from 47 patients with rectal cancer to evaluate the intratumoral het-

erogeneity. In this study 6 patients were excluded due to missing follow up

data. 15 patients showed recurrence during the follow up. DNA from rep-

resentative areas of metastatic tissue was obtained from FFPE specimens

from 11 metastatic rectal cancer patients. Mutations in KRAS codons 12,

13, and 61 were analyzed by the therascreen® KRAS test.

Results: e mean age was 64.13 ± 10.64 years. 19 patients showed a KRAS

mutation. Of the 11 patients with a metastatic disease or local recurrence, 5

patients showed a KRAS mutation. A signicant KRAS mutation status con-

cordance was detected in 81.18% (9/11) of the patients (p=0.03271). Only 2

patients showed intertumoral heterogeneity, which harbored in one patient

a KRAS G12C mutation status in the primary tumor, but a G12V KRAS

mutation status in the corresponding lung lesion, and in the other patient

a G12A mutation in the primary lesion and a WT in the lung metastasis.

Conclusions: We show a signicant concordance of the KRAS mutation

status between tumor samples obtained from the primary tumor and the

metastasis in patients with rectal cancer indicating no relevant intertumoral

heterogeneity. Our data suggest that sampling either the primary or meta-

static lesion is valid for the initial evaluation of KRAS mutation status pre-

dicting the response to anti-EGFR treatment and guiding clinical decisions.

812

Epigenome Mapping Identies Tumor-Specic Gene

Expression in Primary Rectal Cancer

Hannah Flebbe 1; Feda H. Hamdan 1, 2; Vijayalakshmi Kari 1; Julia Kitz 3;

Jochen Gaedcke 1; B. Michael Ghadimi 1; Steven A. Johnsen 2;

Marian Grade 1

1Department of General, Visceral and Pediatric Surgery, University Medical

Center Goettingen, Göttingen, Deutschland

2Gene Regulatory Mechanisms and Molecular Epigenetics Laboratory, Division

of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States

3Institute of Pathology, University Medical Center Goettingen, Göttingen,

Deutschland

Purpose: Epigenetic alterations play a central role in cancer development

and progression (1). e acetylation of histone 3 at lysine 27 (H3K27ac)

specically marks active genes (2). While chromatin immunoprecipita-

tion (ChIP) followed by next-generation sequencing (ChIP-seq) analyses

are commonly performed in cell lines, only limited data are available from

primary tumors. We therefore examined whether cancer-specic alter-

ations in H3K27ac occupancy can be identied in primary rectal cancer

Methods: Tissue samples from primary rectal cancer and matched mucosa

were obtained. ChIP-seq for H3K27ac was performed and dierentially oc-

cupied regions were identied. e expression of selected genes displaying

dierential occupancy between tumor and mucosa were examined in gene

expression data from an independent patient cohort. Dierential expression

of four proteins was further examined by immunohistochemistry.

Results: ChIP-seq for H3K27ac in primary rectal cancer and matched mu-

cosa was successfully performed and revealed dierential binding on 44

regions. is led to the identication of genes with increased H3K27ac, i.e.,

RIPK2, FOXQ1, KRT23, and EPHX4, which were also highly upregulated

in primary rectal cancer in an independent dataset. e increased expres-

sion of these four proteins was conrmed by immunohistochemistry.

Conclusions: is study demonstrates the feasibility of ChIP-seq-based

epigenome mapping of primary rectal cancer and conrms the value of

H3K27ac occupancy to predict gene expression dierences.

References:

1. Markowitz, S.D.; Bertagnolli, M.M. Molecular origins of cancer: Molecular

basis of colorectal cancer. N. Engl. J. Med. 2009, 361, 2449-2460.

2. Rickels, R.; Shilatifard, A. Enhancer Logic and Mechanics in Development and

Disease. Trends Cell Biol. 2018, 28, 608–630

Disclosure Statement: Data has recently been published:

Flebbe, H.; et al. Epigenome Mapping Identies Tumor-Specic Gene Expression

in Primary Rectal Cancer. Cancers 2019; 11(8);1142.

830

Therapy-Dependent Survival in Patients with Colorectal

Peritoneal Carcinomatosis - a Population-Based Study

Patricia Hauer 1; Mareike Mischke 1; Marlene Kaltenstadler 1;

Michael Gerken 2; Pompiliu Piso 3; Monika Klinkhammer-Schalke 2;

Hans Schlitt 1; Matthias Hornung 1

1Klinik und Poliklinik für Chirurgie, Uniklinik Regensburg, Regensburg,

Deutschland

2Tumorzentrum Regensburg, Regensburg, Deutschland

3Klinik für Allgemein- und Viszeralchirurgie, Krankenhaus Barmherzige Brüder

Regensburg, Regensburg, Deutschland

Purpose: Various studies showed a signicant survival benet for cytore-

ductive surgery (CRS) with HIPEC (hyperthermic intraperitoneal chemo-

therapy) compared to surgery and systemic chemotherapy in patients with

peritoneal carcinomatosis (PC). However, a recent prospective randomized

study reported no superiority of CRS and HIPEC to CRS with chemother-

apy, so that now, independent of the CRS, the eectiveness of HIPEC is un-

clear. e aim of this multicenter, retrospective cohort study was the anal-

ysis of treatment-dependent overall survival (OS) aer CRS with HIPEC

compared to surgery and subsequent chemotherapy in patients with PC.

Methods: Based on the clinical cancer registry of the Regensburg Tumor

Center, a retrospective, multicenter cohort study was performed on 941

patients diagnosed with colorectal PC between 2004 and 2018. Primary

endpoint was the therapy-dependent OS estimated using Kaplan-Mei-

er method and multivariable Cox-regression. Risk adjustment was per-

formed for age, sex, primary tumor stage and localization, extraperitoneal

tumor spread, syn- and metachronous PC.

Results: In the included 941 cases, 63 cases were treated with CRS and HIPEC

(6.7%), 176 cases (18.7%) with surgery followed by chemotherapy. Median OS

aer CRS and HIPEC was 40.5 months, aer surgery with chemotherapy 21.4

months. Two-year OS aer CRS and HIPEC was 58.2% (surgery with chemo-

therapy 41.8%); 3-year OS 50.1% and 21.4%, resp. (log rank p<0.001). Aer

risk adjustment, CRS and HIPEC persisted to prove superior to surgery with

chemotherapy (HR 0.529, CI 95% 0.363-0.770, p<0.001). In addition, signi-

cant factors inuencing OS were age, tumor histology and grading, presence

of extraperitoneal metastases, T and N status, onset of PC.

Conclusions: In line with most randomized and retrospective studies to

date, this population-based analysis shows a signicant survival benet of

CRS with HIPEC versus surgery and subsequent chemotherapy.

Disclosure Statement: no conict of interests

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2018

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2018

Gastrointestinal (Noncolorectal) Cancer

Best-of-Abstract-Vorträge

218

FOLFiRI Plus Ramucirumab Versus Paclitaxel Plus

Ramucirumab for Patients with Advanced or Metastatic

Adenocarcinoma of The Stomach or Gastroesophageal

Junction As Second-Line Therapy – Interim Safety and Ecacy

Results from The Phase II Ramiris Study (AIO-STO-0415) of the

German Gastric Group at AIO

Sylvie Lorenzen 1; Peter Thuss-Patience 2; Claudia Pauligk 3; Eray Gökkurt 4;

Thomas J. Ettrich 5; Florian Lordick 6; Michael Stahl 7; Peter Reichardt 8;

Martin Sökler 9; Daniel Pink 10; Stephan Probst 11; Hana Algül 1; Axel Hinke 12;

Thorsten Götze 3; Salah-Eddin Al-Batran 3

1Klinikum rechts der Isar der TU München, München, Deutschland

2Charité-Universitätsmedizin Berlin, Medizinische Klinik m.S. Hämatologie,

Onkologie und Tumorimmunologie, Berlin, Deutschland

3University Cancer Center Frankfurt, Institut für Klinisch-Onkologische

Forschung and IKF Klinische Krebsforschung GmbH am Krankenhaus Nordwest,

Frankfurt/Main, Deutschland

4Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Facharztzentrum

Eppendorf, Hamburg, Deutschland

5Ulm University Hospital, Ulm, Deutschland

6University Cancer Center Leipzig, Leipzig, Deutschland

7Kliniken Essen-Mitte, Essen, Deutschland

8HELIOS Klinikum Berlin-Buch, Berlin, Deutschland

9University Hospital, Tübingen, Deutschland

10Helios Klinikum Bad Saarow, Bad Saarow, Deutschland

11Klinikum Bielefeld, Bielefeld, Deutschland

12CCRC, Düsseldorf, Deutschland

Purpose: Ramucirumab as monotherapy and in combination with pacl-

itaxel is a proven second-line option for advanced gastroesophageal ad-

enocarcinoma (GEA). More and more patients (pts) are pretreated with

docetaxel in the perioperative or rst-line setting. For those pts, the bene-

t of a combination of ramucirumab and paclitaxel is unclear, and physi-

cians would choose an irinotecan-based regimen as second line treatment.

is provides a rationale for the evaluation of FOLFIRI + ramucirumab.

Methods: is is a multicenter, randomized, investigator initiated, phase

II trial, planned to include 111 pts with advanced GEA to receive 2:1 ei-

ther FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel

(days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm

B). Primary endpoint is 6-months OS rate. is abstract displays inter-

im results of safety and overall objective response (ORR) in docetaxel

pre-treated group from up to 65 randomized pts. e results were needed

to decide on conducting a subsequent phase III study.

Results: 58 (A, 36; B, 22) pts were included in the safety analysis and

50 pts with tumor assessment in the response analysis. Main ≥ grade 3

adverse events were respectively in arms A/B: neutropenia (20%/22%),

fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twen-

ty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR

was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate

(DCR) was 65% and 50% for Arm A and B respectively.

Conclusions: e interim safety analysis of the RAMIRIS trial has demon-

strated feasibility of the combination of FOLFIRI and ramucirumab.

Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab

is combined with FOLFIRI, instead of paclitaxel.

455

Pancreatic Tumor Remission in PDX-Models By Treatment

with Gemcitabine in Combination with The Oxathiazine 

GP-2250

Britta Majchrzak-Stiller 1; Marie Buchholz 1; Stefan Hahn 2;

Chris Braumann 1; Waldemar Uhl 1

1Allgemein-u Viszeralchirurgie, St.Josef Hospital Bochum, Bochum, Deutschland

2Ruhr Universität Bochum, ABTEILUNG FÜR MOLEKULARE

GASTROENTEROLOGISCHE ONKOLOGIE, Bochum, Deutschland

Purpose: e oxathiazine GP-2250, a newly dened anti-tumor agent,

displays anti-neoplastic activity on pancreatic cancer tissue as shown both

in cell culture in vitro and in patient derived xenogra (PDX) models in

vivo (1). In the present study, GP-2250 was tested in PDX models in com-

bination with the standard chemotherapeutic agent gemcitabine in view

of a potential antineoplastic synergy of the combination treatment in vivo.

Methods: Using nine dierent PDX models of pancreatic cancer, tumors

were grown up to a size of 200 mm³ in nude mice [NMRI-Fox1 nu/nu]

prior to treatment with 500 mg/kg*BW substance GP-2250 three times a

week and twice a week with 50 mg/kg*BW gemcitabine either alone or in

combination for up to 60 days.

Results: While gemcitabine and GP-2250, given as monotherapy, showed

only a limited antineoplastic response, the combination treatment of

gemcitabine with substance GP-2250 resulted in a signicantly higher

antineoplastic activity than gemcitabine or GP-2250 monotherapy. Eight

out of nine tumors showed a response towards this combination treat-

ment. e tumor growth in ve out of the nine PDX models treated with

the drug combination was characterized by a partial remission via RE-

CIST criteria. ree of the remaining PDX models showed an outcome

of stable disease. Remarkably, in one PDX model, which was immediately

resistant to gemcitabine, the combination therapy nevertheless achieved

a reduction in the tumor growth rate which exceeded that of GP-2250

monotherapy.

Conclusions: e partial remission of pancreatic cancer tumor growth

in mice, which was achieved by the combination of gemcitabine with

GP-2250, is strongly relevant towards clinical practice providing a new

therapeutic strategy in pancreatic cancer treatment. ese results provide

the basis for initial clinical studies with this promising combination of

gemcitabine and GP-2250.

Reference:

1. M. Buchholz et al. Innovative substance 2250 as a highly promising anti-

neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo; BMC

Cancer. 2017 Mar 24; 17(1):216. doi: 10.1186/s12885-017-3204-x

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2018

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2018

Vorträge

802

Classication of Barrett’s Carcinoma Specimens by

Hyperspectral Imaging (HSI)

René Thieme 1; Marianne Maktabi 2; Yannis Wichmann 1;

Thomas Neumuth 2; Andreas Melzer 2; Boris Jansen-Winkeln 1;

Claire Chalopin 2; Ines Gockel 1

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,

Transplantations-, Thorax- und Gefäßchirurgie

2Universität Leipzig, Innovation Center Computer Assisted Surgery (ICCAS)

Purpose: Hyperspectral imaging (HSI) technology combines imaging

with spectroscopy and can be used for the classication of malignant and

non-malignant cells. ereby HSI combined with articial intelligent

algorithms can be used to predict tumor cells in in Barrett’s carcinoma

specimens.

Methods: HSI imaging records light between the visual and near-infra-

red light (500-1000nm). For a rst feasibility study, this technique was

used to discriminate between squamous epithelium and esophageal ad-

enocarcinoma and 45 specimens from Barrett’s carcinoma patients were

recorded. In 22 of the 45 investigated specimens contained also squamous

epithelium. e specimens were xed routinely aer resection in parafor-

maldehyde, were sliced to 3µm, and were stained by haematoxylin and eo-

sin (HE). A non-parametric supervised classication learning algorithm

(K-nearest neighbours (k-NN)) was used for discrimination.

Results: Barrett’s adenocarcinoma cells were recorded by HSI in all 45 in-

vestigated cases. Squamous epithelium and Barrett’s adenocarcinoma cells

displayed dierences in the absorbance between the wave lengths of 500

to 700 nm. For both, the squamous epithelium and the Barrett’s adenocar-

cinoma cells, the intra group variances of the investigated specimens were

quite low. 333,275 and 74,000 spectra could be measured from Barrett’s

adenocarcinoma and from squamous epithelium, respectively. Specicity,

sensitivity and precision with a k-NN (k=5) classier were 0.74, 0.92 and

0.94 for the presence of Barrett’s adenocarcinoma cells.

Conclusions: HE-stained squamous epithelium and Barrett’s adeno-

carcinoma cells showed specic spectral alterations, when measured by

HSI. ese characteristics could be used in the future to develop a com-

puter-assisted algorithm to discriminate semi-automated for tumor cells

Barrett’s carcinoma specimens, which will help to foster decision-making

support in histopathological diagnosis.

Disclosure Statement: None

Poster

117

Alpha Fetoprotein (AFP) Response and Ecacy Outcomes in

the Phase 3 Celestial Trial of Cabozantinib (C) Versus Placebo

(P) in Advanced Hepatocellular Carcinoma (HCC)

Oliver Waidmann 1; R.K. Kelley 2; L. Rimassa 3; B.-Y. Ryoo 4; J.-F. Blanc 5;

S.L. Chan 6; V. Zagonel 7; T. Yau 8; S. Sen 9; D.W. Markby 9; R. Kaldate 9;

A.B. El-Khoueiry 10

1Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland

2UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,

United States

3Humanitas Research Hospital, Milano, Italien

4Asan Medical Center University of Ulsan College of medicine, Seoul, Südkorea

5Hospital Haut Leveque, Pessac, Frankreich

6Prince of Wales Hospital Shatin, Hong Kong

7Istituto di Ricovero Cura a Carattere Scientico Istituto Oncologico Veneto,

Padova, Italien

8Queen Mary Hospital, Hong Kong

9Exelixis Inc, South San Francisco, United States

10USC Norris Comprehensive Cancer Center, Los Angeles, United States

Purpose: AFP response, dened as a decrease in serum levels of the tu-

mor marker AFP aer therapy, has been associated with improved sur-

vival of patients (pts) with HCC treated with locoregional therapy; high

baseline (b) AFP levels are associated with poor prognosis. In the phase 3

CELESTIAL trial (NCT01908426), C signicantly improved overall sur-

vival (OS) and progression-free survival (PFS) vs P in pts with previously

treated advanced HCC. Here we evaluate clinical outcomes with C in the

CELESTIAL trial based on AFP response or progression on treatment.

Methods: 707 pts were randomized 2:1 to receive C (60 mg qd) or P. El-

igible patients had a pathologic diagnosis of HCC, Child-Pugh score A,

and ECOG PS ≤1. Pts received prior sorafenib and up to 2 lines of prior

systemic therapy for HCC. Serum AFP levels were measured centrally at

b and every 8 weeks thereaer. Outcomes were evaluated for pts with ele-

vated b serum AFP (≥20 ng/mL) based on AFP response (≥20% decrease

from b) or progression (≥20% increase from b) at week 8.

Results: Overall, 331 pts (70%) in the C arm and 160 (68%) in the P arm

had elevated b AFP levels, and 236 (50%) and 111 (47%), respectively,

were evaluable for AFP response at Week 8. Among evaluable pts, 117 pts

(50%) in the C arm vs 14 (13%) in the P arm had an AFP response and 72

(31%) vs 75 (68%), respectively, had AFP progression. Median OS with C

was 16.1 mo for AFP responders vs 9.1 mo for non-responders (HR 0.61,

95% CI 0.45-0.83), and median PFS with C was 7.3 mo vs 4.0 mo (HR

0.55, 95% CI 0.41-0.75). For pts with AFP progression, median OS with C

was 8.1 mo, and median PFS with C was 3.6 mo. Hazard ratios for OS and

PFS with C also favored AFP responders over non-responders when ana-

lyzed according to best response through week 24 or using 50% decrease

from b as the cuto for response.

Conclusions: AFP response rate was higher with C vs P, and AFP response

was associated with longer OS and PFS with C for pts with previously

treated advanced HCC. Response assessment in HCC may be improved

by evaluating on-treatment AFP changes in addition to radiographic

response.

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2018

171

Association of Adverse Events (AES) with Eciacy Outcomes

for Cabozantinib (C) in Patients (PTS) with Advanced

Hepatocellular Carcinoma (AHCC) in the Phase 3 Celestial Trial

Oliver Waidmann 1; G.K. Abou-Alfa 2; T. Meker 3; A.-L. Cheng 4; I. Cicin 5;

L. Bolondi 6; H.J. Klümpem 7; S.L. Chan 8; V. Dadduzio 9; S. Milwee 10;

S. Dubey 2; R.K. Kelley 11; A.B. El-Khoueiry 12

1Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland

2Memorial Sloan-Kettering Cancer Center, New York, United States

3University College London Hospital, London, United Kingdom

4National Taiwan University Hospital, Taipei, Taiwan

5Trakya University Hospital, Erdime, Turkey

6Universität Bologna, Bologna, Italien

7Amsterdam University Medical Centre, University Amsterdam, Amsterdam,

Niederlande

8State Key Laborotory of oncolocgy, Chinese University of Hong Kong,

Hong Kong

9Institute Oncology Veneto, Padova, Italien

10Exelixis Inc, South San Francisco, United States

11UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,

United States

12USC Norris Comprehensive Cancer Center, Los Angeles, United States

Purpose: Class-specic AEs occurring with tyrosine kinase inhibitors

have been associated with improved ecacy outcomes in several tu-

mor types including aHCC. In the CELESTIAL trial C improved overall

survival (OS) and progression-free survival (PFS) vs placebo (P) in pts

with previously treated aHCC. Here, we retrospectively evaluate the as-

sociation of palmar-plantar erythrodysaesthesia (PPE) and hypertension

(HTN) with OS and PFS for C in the CELESTIAL trial.

Methods: 707 pts with aHCC were randomized 2:1 to receive 60 mg C

or P once daily. Eligible pts had Child-Puqh score A, ECOG PS ≤1, must

have received prior sorafenib and could have received up to two prior reg-

imens of systemic therapy for HCC. OS and PFS with C were evaluated

for pts with any grade PPE or ≥ grade 3HTN within the rst 8 weeks of

study treatment.

Results: Overall, 374 (80%) pts in the C arm and 179 (76) pts in the P

arm completed ≥ 8 weeks of treatment. In the rst 8 weeks, 188 (40%) of

C-treated pts developed any grade PPE vs 11 (5%) of P-treated pts and 61

(13%) of C-treated pts developed grade ≥3 HTN vs 3 (1%) of P-treated

pts. Median OS with C was 14.4 mo for pts with any grade PPE vs 3.4 mo

for pts without PPE (HR 0.59, 95% CI 0.47-0.74) and median PFS with C

was 6.5 mo vs 3.7 mo, respectively (HR 0.63,95% CI 0.51-0.78). Median

OS with C was 16.1 mo for pts with grade ≥3 HTN vs 9.5 mo for pts

without grade ≥3 HTN (HR 0.56, 95 CI 0.39-0.80), and median PFS with

C was 7.4 mo vs 4.4 mo, respectively (HR 0.59, 95% CI 0.43-0.82). Some

imbalances in baseline (BL) characteristics were present. Pts with PPE had

better ECOG PS (60% vs 47% ECOG 0), better liver function (48% vs 34%

ALBl grade 1), and less macrovascular invasion (24% vs 30%) than those

without. Likewise, pts with grade ≥3 HTN had better ECOG PS (61% vs

51% ECOG 0), better liver function (56% vs 37% ALBI grade 1), and less

macrovascular invasion (20% vs 29%) than those without.

Conclusions: e development of PPE or grade ≥3 HTN with C was as-

sociated with prolonged OS and PFS in pts with previously treated aHCC

although some imbalances in BL characteristics between comparator

qroups were present.

172

Matching-Adjusted Indirect Comparison of Cabozantinib (C)

Versus Regorafenib (R) in Advanced Hepatocellular Carcinoma

(HCC)

Marino Venerito 1; R.K. Kelley 2; P. Mollon 3; J.-F. Blanc 4; B. Daniele 5, 6; T. Yau 7;

A.-L. Cheng 8; V. Valcheva 9; A. Remiro Azocar 10; G. Baio 10; Y. LI 11;

G.K. Abou-Alfa 12

1Universitätsklinikum Magdeburg , Magdeburg, Deutschland

2UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,

United States

3Ipsen Pharma SAS, Boulogne-Billancourt

4Hospital Haut Leveque, Bordeaux, Frankreich

5G. Rummo Hospital, Benevento, Italien

6Ospedale del Mare, Napoli, Italien

7University of Hong Kong, Hong Kong, Hong Kong

8National Taiwan University Hospital, Taiwan

9IPSEN, Boulogne-Billancourt, Frankreich

10University College London, London, United Kingdom

11IQVIA World Publications Ltd., London, United Kingdom

12Memorial Sloan-Kettering Cancer Center, New York, United States

Purpose: C and R have demonstrated survival benet in second-line

treatment of advanced HCC. e aim of this matching-adjusted indirect

comparison (MAIC) was to compare the safety and ecacy of C and R

for patients with HCC who have received sorafenib (S) as the only prior

systemic therapy.

Methods: Data from two pivotal trials with C (CELESTIAL (CT) or R

(RESORCE (RT)) in patients with HCC were used. Using MAIC, indi-

vidual-level data (ILD) from patients enrolled in CT who had received

S as the sole prior therapy (N=495) were adjusted to match the average

baseline (BL) characteristics of the 573 patients enrolled in RT, for which

ILD are not available. To compare survival outcomes, ILD were simulated

for regorafenib using the published Kaplan-Meier (KM) curves for the RT.

Parametric distributions were tted to the ILD to model progression-free

survival (PFS) and overall survival (OS). Grade 3/4 treatment-emergent

drug-related adverse events (AEs) aecting >5% of patients in any arm of

either CT or RT were compared.

Results: Aer balancing BL characteristics, the weighted KM curves for

patients receiving C or R were associated with a median (95% Condence

Interval) PFS of 5.59 (4.90–7.26) months and 3.19 (2.78–4.14) months,

respectively (p<0.05, log-rank test); median OS were 11.37 (8.90–16.95)

months for C and 10.79 (9.18–12.30) months for R (p>0.05, log-rank test).

Upon tting and extrapolating the selected models, C treatment was as-

sociated with longer median PFS and OS than R. e median PFS esti-

mate was 5.49 (4.92–6.13) months for C vs 3.39 (3.05–3.78) months for R,

median OS was 11.40 (10.01–12.96) months for C vs 10.29 (9.15–11.56)

months for R. R was associated with lower rates of diarrhea.

Conclusions: In patients who received second-line treatment aer S and

were matched for BL characteristics, C was associated with prolonged me-

dian PFS and OS compared with R, whereas R was associated with low-

er rates of diarrhea than C. However, even aer matching, bias may still

occur in MAIC due to imbalance in unobserved factors, and it cannot

replace a head-to-head randomized control trial.

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174

Quality-Adjusted Life Years Accrued with Cabozantinib in

Patients with Advanced Hepatocellular Carcinoma (AHCC)

in the CELESTiAL Trial

Marino Venerito 1; G.K. Abou-Alfa 2; P. Mollon 3; T. Meyer 4; A.-L. Cheng 5;

A.B. El-Khoueiry 6; R.K. Kelley 7; A.D. Baron 8; F. Benzaghou 9; V. Valcheva 3;

S. Hazra 10; M. Mangeshkar 10; N. Freemantle 4

1Universitätsklinikum Magdeburg, Magdeburg, Deutschland

2Memorial Sloan-Kettering Cancer Center, New York, United States

3Ipsen Pharma SAS, Boulogne-Billancourt, Frankreich

4University College London, London, United Kingdom

5Staatliche Universität Taiwan, Taipei, Taiwan

6Norris Comprehensive Cancer Center, Los Angeles, United States

7UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco,

United States

8California Pacic Medical Center, San Francisco, United States

9Ipsen Innovation, Les Ulis, Frankreich

10Exelixis Inc, South San Francisco, United States

Purpose: In patients previously treated for aHCC, cabozantinib (C) led

to longer overall survival and progression-free survival vs placebo (P)

in the randomized, phase 3 CELESTIAL trial (NCT01908426; N=707).

CELESTIAL was stopped early for benet at the second interim analysis.

is post hoc analysis estimated the incremental quality-adjusted life

years (QALYs) accrued in CELESTIAL.

Methods: Health utility was elicited at each study visit using the EQ-

5D-5L quality of life questionnaire. (completed by 82-100% of patients

overall). UK crosswalk taris were applied for health states. Cumulative

QALYs by patient were calculated by linear interpolation; for patients who

were censored (31% of patients; including 9% within 100 days of random-

ization), the last observed utility value was carried forward to study end.

e dierence in restricted mean QALYs was calculated using generalized

linear models, accounting for baseline utility, and with 0.06-0.08 QALYs

considered the minimal important dierence.

Results: At day 50 aer randomization (acute treatment phase), C was

associated with a small reduction in mean total QALYs vs P (dierence

−0.003; 95% CI −0.005 to −0.002; p≤0.001; n=601 [C n=389; P n=212]).

At day 100, there was a numerical benet in mean total QALYs for C

(dierence +0.007; 95% CI −0.001 to 0.015; p=0.103; n=627 [C n=410; P

n=217]), and at day 150 the dierence was +0.032 QALYs (95% CI 0.017

to 0.047; p≤0.001; n=629 [C n=412; P n=217]) in favor of C. Over the en-

tire follow-up, patients randomized to C accrued a mean of +0.092 (95%

CI 0.016 to 0.169; p=0.018; n=700 [C n=465; P n=235]) additional QA-

LYs compared with those receiving P. Using alternative Devlin weights for

health states, the mean accrued QALYs with C was +0.115 vs P (95% CI

0.032 to 0.198; p=0.007).

Conclusions: Cabozantinib was associated with an initial, small reduc-

tion in health utility. However, with continued treatment, health utility

increased and at the end of the study there was a clinically and statistically

signicant benet in mean QALYs in favor of C.

199

Pet-Directed Combined Modality Therapy for

Gastroesophageal Junction Cancer: First Results of the

Prospective Memori Trial

Sylvie Lorenzen 1; Quante Michael 2; Isabell Rauscher 3;

Julia Slotta-Huspenina 4; Karl-Friedrich Becker 4; Wilko Weichert 4;

Markus Feith 5; Julian Holch 6; Helmut Friess 5; Stephanie Combs 7;

Wolfgang Weber 3; Bernhard Haller 8; Martin Angele 9;

Markus Albertsmeier 9; Christiane Blankenstein 10; Stefan Kaspar 11;

Jens Zimmermann 2; Hana Algül 2; Roland Schmid 2; Markus Schwaiger 3;

Jens Siveke 11

1Technical University Munich, Klinikum rechts der Isar, III. Medizinische Klinik

und Poliklinik, Munich, Deutschland

2Technical University Munich, Klinikum rechts der Isar, II. Medizinische Klinik

und Poliklinik, Munich, Deutschland

3Technical University Munich, Klinikum rechts der Isar, Department of Nuclear

Medicine, Munich, Deutschland

4Technical University Munich, Institute of Pathology, Munich, Deutschland

5Technical University Munich, Klinikum rechts der Isar, Surgical Clinic and

Policlinic, Munich, Deutschland

6Ludwig-Maximilians-Universität München, Department of Medicin III,

München, Deutschland

7Technical University Munich, Klinikum rechts der Isar, Department of Radiation

Oncology, Munich, Deutschland

8Technical University Munich, Klinikum rechts der Isar, Institut für Medizinische

Informatik, Statistik und Epidemiologie, Munich, Deutschland

9Ludwig Maximilian University, Department of General, Visceral and

Transplantation Surgery, Munich, Deutschland

10Technical University Munich, Muenchener Studienzentrum, Munich,

Deutschland

11University Hospital Essen, West German Cancer Center, Division of Solid Tumor

Translational Oncology, DKTK partner site Essen, Deutschland

Purpose: We evaluated a PET-guided treatment stratication for

improvement in obtaining negative surgical margins (R0) in resectable

gastroesophageal junction (GEJ) adenocarcinoma. According to

sequential18F-FDG PET, only 40–50% of patients (pts) respond to

neoadjuvant chemotherapy (CTX). Early PET non-responders (P-NR)

aer induction CTX might benet from chemoradiation (CRT).

Methods: 75 pts with resectable GEJ adenocarcinomas were enrolled in

this interventional, prospective, non-randomized multicenter trial. Pts

underwent baseline 18F-FDG PET scan followed by 1 cycle of CTX (e.g.

EOX, XP, mFOLFOX6). PET was repeated at day 14-21 and responders

(P-R), dened as ≥ 35% decrease in SUVmaxfrom baseline, continued

with CTX. P-NR switched to CRT (41.4 Gy/23 fractions with weekly car-

boplatin/paclitaxel). Pts underwent surgery 4-6 weeks post-CTX/CRT.

Primary objective was improvement of R0 resection rates in P-NR above

a proportion of 70% based on results from the MUNICON1/2 trials. Sec-

ondary endpoints include disease-free survival (DFS), overall survival

(OS), and translational endpoints.

Results: 160 pts with resectable GEJ adenocarcinomas were screened

with PET in three German university centers. Overall, 85 pts (53%) could

not be included due to previously undetectable metastases (40/25%), no

or too low FDG uptake of the primary tumor (21/13%), other reasons

(24/15%). 75 eligible pts were enrolled in the study and 69 were evaluable.

Based on PET criteria, 47 (68%) and 22 (32%) were P-R and P-NR, respec-

tively. R0 resection rates were 94% (44/47) for P-R and 91% (20/22) for

P-NR. Pathologic complete remission (pCR; <10% vital tumor cells), was

33% (15/46) in P-R and 55% (12/22) in P-NR. With a median follow-up

time of 19 months (mo), estimated 18 mo DFS was 71%/61% for P-R/

P-NR, respectively. Observed median 18 mo OS was 95% for P-R and 75%

for P-NR.

Conclusions: Alternative CRT for GEJ adenocarcinoma improved R0-

and pCR rates among pts who were P-NR aer induction CTX. PET re-

sponse was prognostic for a prolonged OS and DFS.

Disclosure Statement: No conicts of interest

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220

Does Inammation or Malignancy have Specic Impact onto

the Early Postoperative Outcome – Comparison of Pylorus-

Preserving Pancreatic Head Resection by Traverso-Longmire

in Chronic Pancreatitis vs. Cancer of the Pancreatic

Head – Initial Results of a Tertiary Center

Nikolas Scholz 1; Max Grabowski 1; Ronny Otto 2; Roland S. Croner 1;

Henry Ptok 2; Frank Meyer 1

1Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke

University at Magdeburg, Magdeburg, Deutschland

Purpose: To investigate the impact of various diagnoses (chronic pan-

creatitis [“Pan.“] vs. cancer of the pancreatic head [“Ca“]) & interindiv.

dierences such as age & accompanying diseases onto the early postop.

outcome in comparable interventional invasiveness, surgical trauma &

surgical intervention(Op)-induced SIRS-associated alterations.

Methods: All consecutive pats. who had undergone Op in Pan. & Ca were

registered & various outcome parameters such as postop. morbidity (gen-

eral/specic complication rates) & 30-d-mortality were determined.

Results: From 2003-2015, overall 315 pats. were registered out of whom

only n=295 (sex ratio: m/w=181:114 [1.59:1]; median age: 59 [range: 20-

82] yrs.) could be evaluated - 197 cases with Ca (66.8%) & 98 individu-

als with Pan. (33.2%). In comparison, median age was 68.5 (37-82) vs. 51

(20-72) yrs. in Ca & Pan. (p<0.001), resp.; mean ASA scoring was 2.3 (Ca

[1-4]) & 2.1 (Pan. [1-4]; p=0.084), resp. Median preop. hospital stay was 2

[0-17] d in both diseases whereas median postop. stay was 18 (Ca [2-88])

& 15 (Pan. [6-48]) d, resp. (p=0.029).

Surprisingly, there were similar general & specic complication rates

of 21.3% (Ca) vs. 21.4% (Pan.) & 40.1% (Ca) vs. 43.9% (Pan.) (p=0.274;

p=0.616), resp.; in addition, there was only a marginal dierence of the

30-d-mortality: 3.6% (Ca) vs. 2.0% (Pan.) (p=0.723).

Univariate analysis resulted in ASA class with a signif. impact onto mor-

bidity (p=0.013).

In pats. with postop. morbidity, the No. of intraop. transfused red cell

packs was signif. greater than in subjects with no morbidity (1.156

vs. 0.304; p=0.000). Morbidity itself had a signif. eect onto mortality

(p=0.000).

Multivariate analysis using logistic regression did not show any signif.

associations.

Conclusions: e initially hypothesized disadvantageous impact of a

malignancy compared with chronic inammation can not be conrmed

based on the morbidity & mortality despite signif. older pats. & a longer

postop. hospital stay.

Disclosure Statement: e authors do not have anything to be disclosed.

221

Does Splenectomy Play a Signicant Role in the Surgical

Outcome of Gastric Cancer?

Ingo Gastinger 1; K. Heine 1; Frank Meyer 2; Ronny Otto 1; Stefanie Wol 2;

Roland S. Croner 2

1AN-Institut für Qualitätssicherung in der operativen Medizin, Otto-von-

Guericke-Universität, Magdeburg, Deutschland

2Klinik für Allgemein-, Viszeral-, Gefäüß- und Transplantationschirurgie,

Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland

Purpose: Splenectomy can be associated with an increase of postop.

complications but a worse 5-yr survival.

Methods: From 01/01/2007-12/31/2009, all patients (nin total=2,897; surgi-

cal depts., n=141) with primary gastric Ca/Tu lesion of the esophagogas-

tric junction (AEG-Tu) who underwent surgery were registered.

Results: Overall, 2,545 patients (=group[gr.] 1) underwent Tu resection.

Gr.2/3/4/5: AEG-Tu (n=475)/distal gastric Ca (n=2,070)/intraop. spleen

injury (n=127)/splenectomy (n=94) due to Tu inltration vs. injury.

Splenectomy rate was 11.1% (n=283) with the highest proportion in AEG-

Tu (19.4%; no signif. dierences among the groups regarding age, sex ratio

& ASA).

Surgical procedures: e highest splenectomy rate was found in transhia-

tally ext. gastrectomy (in total, 30.2%; AEG-Tu, 27.3%; distal gastric Ca,

38.6%).

Morbidity in case of splenectomy was higher overall & depending on Tu

site (the same in general postop. complication rate; specic postop. compli-

cation rate, no dierence).

Lethality post-splenectomy: Only in AEG-Tu, it was signif. higher (15.2

vs. 5.0%).

All splenectomized patients showed a shorter long-term survival (p<0.001;

18 vs. 36 months with preservation of the spleen).

e lowest 5-yr-survival rates were observed in splenectomized AEG-Tu

patients (25%) & in those with splenectomy due to Tu inltration (20%).

Logistic regression: Spleen preservation – signif. independent variable

regarding lower postop. morbidity whereas splenectomy was associated

with higher postop. complication rate. Overall, splenectomy did not pro-

vide a signif. impact onto lethality. However, splenectomy as part of resec-

tion in AEG-Tu was associated with a signif. higher lethality. A tendential

impact of splenectomy onto a lower overall survival was only seen in the

group of AEG-Tu.

Conclusions: Splenectomy – negative predictor for a worse early postop.

& long-term oncosurgical outcome; therefore, it can only be justied by

direct Tu inltration or irreparable spleen injury.

Disclosure Statement: ere is nothing to be disclosed.

367

Anal Cancer – Population-Based Data from the Munich

Cancer Registry

Anne Schlesinger-Raab 1; Claudia Hörl 2; Heinrich Schorer 3; Claus Belka 4;

Stephanie Combs 5; Reinhard Ruppert 6; Jens Werner 7; Helmut Friess 8;

Jutta Engel 9

1Tumorregister München am Klinikum der Universität München, Institut für

Medizinische Informationsverarbeitung Biometrie und Epidemiologie, Ludwig-

Maximilians-Universität München, München, Deutschland

2Gemeinschaftspraxis für Strahlentherapie und Radioonkologie am Klinikum

Schwabing, München, Deutschland

3Gemeinschaftspraxis für Strahlentherapie am Klinikum Harlaching -

Bogenhausen - Neuperlach, München, Deutschland

4Klinik und Poliklinik für Strahlentherapie und Radioonkologie am Klinikum der

Universität München, Ludwig-Maximilians-Universität München, München,

Deutschland

5Klinik und Poliklinik für RadioOnkologie und Strahlentherapie, Klinikum Rechts

der Isar, Technische Universität München, München, Deutschland

6Klinik für Proktologie und Chirurgie, München Klinik Neuperlach, München,

Deutschland

7Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der

Universität München, Ludwig-Maximilians-Universität, München, Deutschland

8Klinik und Poliklinik für Chirurgie, Klinikum Rechts der Isar, Technische

Universität München, München, Deutschland

9Tumorregister München, Bayerisches Krebsregister - Regionalzentrum

München (LGL) am Klinikum der Universität München, Institut für Medizinische

Informationsverarbeitung Biometrie und Epidemiologie, Ludwig-Maximilians-

Universität, München, Deutschland

Purpose: Anal cancer is rare and linked to HPV infections similar to cer-

vical and some oropharyngeal cancers. In Germany, the incidence diers

clearly between men and women (1.3/100,000 vs. 2.0/100,000). Objective

was to reveal sex-related dierences.

Methods: e number of anal cancer diagnoses between 1998 and 2016

registered in the catchment area of the Munich Cancer Registry were

analyzed by sex, and prognostic factors. Cumulative incidence of tumor

progression, and secondary tumors in consideration of competing risks as

well as survival analyses by Kaplan-Meier method and multivariate Cox

regression analysis were conducted.

Results: A total of 1 815 malignant anal tumors were recorded. Aer exclu-

sion of in situ cases, mucosal and skin melanomas, lymphomas, sarcomas,

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2018

and neuroendocrine neoplasia the age-adjusted incidence (European

Standard Population) was 1.2/100,000 in men and 2.0/100,000 in women

without changes since 1998. Excluding death certicate only cases, 1 564

invasive anal carcinoma were nally analyzed. Median age at initial diag-

nosis accounted for 65.1 years, men were 2 years younger than women.

Age and male/female ratio of 1:2 did not change over the observed time.

TNM-categories were similar frequent in men and women. Whereas G3

tumors were signicantly more in women (39% vs. 28%) and adenocarci-

nomas were more in men (7.8% vs 3.2%).

Conclusions: Women have a better outcome in anal cancer; although no

tumor-specic characteristics were attributed to this dierence.

404

Induction Chemotherapy in Locally Advanced Pancreatic

Cancer (LAPC) - Final Results of a Multicenter Randomized

Phase 2 AIO Trial (NEOLAP)

Ingo Hartlapp 1; Hana Algül 2; Eray Gökkurt 3; Gabriele Siegler 4;

Uwe Martens 5; Dirk Waldschmidt 6; Uwe Pelzer 7; Elke Hennes 8;

Martin Fuchs 9; Jens Siveke 10; Frank Kullmann 11; Stefan Böck 12;

Thomas J. Ettrich 13; Peter Ferenczy 14; Ralph Keller 15;

Christoph-Thomas Germer 16; Hubert Stein 17; Ingo Klein 16;

Volker Heinemann 18; Volker Kunzmann 1

1Uniklinik Würzburg, Medizinische Klinik II, Internistische Onkologie, Würzburg,

Deutschland

2Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar TU München,

München, Deutschland

3Hematology-Oncology Practice Eppendorf (HOPE), Hamburg, Deutschland

4Paracelsus Medizinischen Universität Nürnberg, Klinik für Innere Medizin 5,

Schwerpunkt Onkologie / Hämatologie, Nürnberg

5SLK-Kliniken Heilbronn GmbH, Klinik für Innere Medizin III: Hämatologie,

Onkologie, Palliativmedizin, Heilbronn, Deutschland

6Uniklinik Köln, Klinik für Gastroenterologie und Hepatologie, Köln, Deutschland

7Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Medizinische Klinik

mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie (CVK),

Berlin

8Überörtliche Gemeinschaftspraxis Schwerpunkt Hämatologie, Onkologie und

Palliativmedizin , MVZ Onkologie Barmbek, Hamburg, Deutschland

9München Klinik Bogenhausen, Klinik für Gastroenterologie, Hepatologie und

Gastroenterologische Onkologie , München

10West German Cancer Center, University Hospital Essen, Essen

11Klinikum Weiden, Medizinische Klinik I, Weiden

12Klinikum der Universität München, Medizinische Klinik und Poliklinik III,

München

13Universitätsklinikum Ulm, Klinik für Innere Medizin I, Ulm

14Clin Assess Gesellschaft für Klinische Forschung GmbH, Leverkusen

15AIO-Studien-gGmbH, Berlin, Deutschland

16Uniklinik Würzburg, Chirurgische Klinik I, Würzburg , Deutschland

17Paracelsus Medizinische Universität Nürnberg, Klinik für Allgemein-, Viszeral-

und Thoraxchirurgie, Nürnberg, Deutschland

18Klinikum der Universität München, Medizinische Klinik und Poliklinik III,

München, Deutschland

Purpose: e best preoperative treatment for LAPC is unknown. NEO-

LAP is the rst prospective, randomized trial to compare nab-Paclitaxel

and Gemcitabine (nPG) with FOLFIRINOX-based induction chemother-

apy in LAPC.

Methods: In this open-label, randomized, two-arm, phase 2 trial, treat-

ment-naive patients (pts) with histologically/cytologically proven non-re-

sectable LAPC were recruited from 33 German centers. Aer two cycles

of nPG induction pts without progressive disease or unacceptable adverse

events (AEs) were randomly allocated (1:1) to receive either two addition-

al cycles of nPG or four cycles of sequential un-modied sqFOLFIRINOX.

Secondary resectability was assessed by surgical exploration in all pts with

at least stable disease (SD) aer completion of induction chemotherapy.

e primary endpoint was conversion rate (R0/R1 resection). Secondary

endpoints included overall survival (OS), safety, CA 19-9 response and

central radiological review.

Results: 168 pts were registered and 130 were randomly allocated (64

to nPG and 66 to sqFOLFIRINOX). Conversion rate was 30.6 vs 45.0%

(Odds ratio 0.54; 95% CI, 0.26 to 1.13; P = 0.135), OS 17.3 vs 22.5 months

(adjusted HR 0.73; 95% CI, 0.42 to 1.28; P = 0.268), AEs ≥ grade 3 54,7 vs

53,0%, (investigator assessed) ORR 22.6 vs 21.7%; DCR 82.3 vs 75.0%, CA

19-9 response (baseline to week 16); -62.2 % vs -56.7 %, major pathologi-

cal response (<10% viable tumor cells) 15 vs 9.5% in the nPG (n=62) and

sqFOLFIRINOX (n=60) arm, respectively. Among all ITT-pts (N=165)

conversion was associated with signicant improved OS (27.4 vs. 14.2

months; P = 0.0035). First results from central radiological review with

regard to primary and secondary resectability status and tumor response

will be presented.

Conclusions: Secondary resection aer 4 months of induction chemo-

therapy followed by surgical exploration is feasible in about 1/3 of pts with

LAPC and associated with markedly prolonged OS without signicant

dierence in safety or ecacy endpoints between nPG and sqFOLFIRI-

NOX arm.

Disclosure: Supported by Celgene + AIO-Studien-gGmbH

433

Immunohistochemical Proling of Liver Metastases and

Matched-Pair Analysis in Patients with Metastatic Pancreatic

Ductal Adenocarcinoma

Thomas Held 1; Caroline S. Verbeke 2; Oliver Strobel 3; Wiktor Rutkowski 4;

Christina Villard 5; Carlos Fernández Moro 6; Marco Del Chiaro 5;

Markus Büchler 3; Matthias Löhr 4

1Department of Radiation Oncology, Heidelberg University Hospital,

Heidelberg, Deutschland

2Institute of Clinical Medicine, University of Oslo, Oslo, Norwegen

3Department of General, Visceral and Transplantation Surgery, Heidelberg

University Hospital, Heidelberg, Deutschland

4Department of Clinical Intervention and Technology (CLINTEC), Karolinska

Institute, Stockholm, Schweden

5Department of Cancer, Karolinska University Hospital, Stockholm, Schweden

6Department of Pathology, Karolinska University Hospital, Stockholm,

Schweden

Purpose: e purpose of the current study was to investigate the immu-

nohistochemical (IHC) prole of liver metastases (LM) from patients with

pancreatic ductal adenocarcinoma (PDAC).

Methods: Liver biopsies from seventy-seven (n = 77) patients with PDAC

diagnosed between 2010 and 2014 were evaluated regarding expression of

15 IHC markers. In a separate subgroup analysis (n = 12), paired samples

(LM and primary tumor) from the same patient were investigated for dis-

cordance in the IHC prole.

Results: LM were classied as pancreatobiliary-type (PB-type) in 72

cases (93.5%), intestinal-type (INT-type) in four cases (5.2%) and squa-

mous in one case (1.3%). ere was no signicant dierence in overall

survival (OS) between LM of PB-type or INT-type (p = 0.097). In multi-

variate analysis, age < 70 years (p = 0.047), absence of SMAD4 mutation

(p = 0.026), absence of CDX2 expression (p = 0.003) and well to mod-

erate dierentiation were signicant prognostic factors for better OS in

patients with LM (p = 0.031). Analysis of paired tissue samples from LM

and primary tumor revealed marked discordance in CDX2 (50% gained,

p = 0.125) and SMAD4 (33% loss of SMAD4, p = 0.375).

Conclusions: CDX2 expression and SMAD4 mutation indicate poor out-

come in patients with LM of PDAC. Matched-pair analysis reveals discor-

dance in expression of distinct IHC markers.

References:

Not applicable.

Disclosure Statement: e authors declare no conicts of interest.

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444

Patient with Severe Symptomatic Aortic Valve Insuciency

and Multiple Small Strokes Due to Nonbacterial Thrombotic

Endocarditis (NBTE) Diagnosed with Metastatic Pancreatic

Cancer

Maike Collienne 1, 2; Martin Kuhns 2, 3; Hans-Peter Hauber 2, 4; Dirk Arnold 1

1Onkologie mit Sektion Hämatologie, Asklepios Klinik Altona, Hamburg,

Deutschland

2Antibiotic Stewardship-Team, Asklepios Klinik Altona, Hamburg, Deutschland

3Fachgebiet Mikrobiologie, Medilys Laborgesellschaft mbH, Hamburg,

Deutschland

4Kardiologie, Pneumologie und internistische Intensivmedizin, Asklepios Klinik

Altona, Hamburg, Deutschland

Purpose: Patients with metastatic cancer diseases tend to have a hyperco-

agulopathy with risk of thrombosis, arterial embolization and, in conse-

quence, ischemic strokes. One of the known causes is NBTE.

Methods/Patient characteristics: A 51-year old athletic man with

metastatic pancreatic adenocarcinoma presented with aphasia and

memory gaps for four days aer initiation of chemotherapy (FOLFIRINOX

regimen).

Results: A cerebral MRI showed a pattern of multiple small ischemic le-

sions. A transesophageal echocardiography revealed a severe aortic valve

insuciency with mobile vegetation. An empiric antibiotic treatment

with ampicillin, ucloxacilline and gentamicin was initiated. e patient

had to undergo biological aortic valve replacement. As a possible source of

infection, the port catheter was removed. Microbiology showed no patho-

logical evidence of infective endocarditis. erefore, the duration of an

antibiotic treatment was limited to 22 days.

Pre-medical history showed that the patient already had previous periph-

eral venous thrombosis one month ago. During the current treatment,

multiple thrombophlebitic events occurred despite anticoagulation. Fur-

ther inspections regarding dierent causes of NBTE showed no patholog-

ical ndings. However, a histopathological examination of the aortic valve

had not been done.

During the management period, CA19-9 levels rose and CT scan showed

disease progression of the pancreatic tumor and the hepatic metastases.

erefore, chemotherapy was re-induced and a new port catheter was im-

planted.

Conclusions: is is a rare but manageable consequence of paraneoplastic

hypercoagulopathy in metastatic pancreatic cancer despite oral

anticoagulation.

Disclosure Statement: e authors have no conict of interest.

452

Analysis of Central versus Local Deviating HER2 Test Results

in Gastric Cancer in the Multicenter Varianz Study

Katharina Kolbe 1; Ivonne Haner 1; Katrin Schierle 2; Dieter Maier 3;

Birgitta Geier 3; Birgit Luber 4; Albrecht Kretzschmar 5;

Ludwig Fischer von Weikersthal 6; Miriam Ahlborn 7; Jorge Riera 8;

Beate Rau 9; Gabriele Siegler 10; Stefan Fuxius 11; Thomas Decker 12;

Christian Wittekind 2; Florian Lordick 1

1UCCL, Universitätsklinikum Leipzig, Leipzig, Deutschland

2Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

3Biomax Informatics AG, Planegg, Deutschland

4Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische

Universität München, München, Deutschland

5Internistische Onkologie und Hämatologie, Klinikum St. Georg Leipzig,

Leipzig, Deutschland

6 Praxis für Hämatologie und Internistische Onkologie, Klinikum St. Marien

Amberg, Amberg, Deutschland

7Hämatologie & Onkologie, Kllinikum Braunschweig, Braunschweig,

Deutschland

8Klinik für Hämatologie, Onkologie und Palliativmedizin, Universitätsklinikum

Marburg, Marburg, Deutschland

9Chirurgische Klinik Campus Charité Mitte / Campus Virchow-Klinikum

CCM/CVK , Charité Berlin, Berlin, Deutschland

10Innere Medizin Onkologie / Hämatologie, Klinikum Nürnberg Nord, Nürnberg,

Deutschland

11Onkologische Schwerpunktpraxis Heidelberg am Römerkreis, Heidelberg,

Deutschland

12Gemeinschaftspraxis für Hämatologie und Onkologie GbR, Wangen im Allgäu,

Deutschland

Purpose: VARIANZ is a non-interventional study funded by BMBF

(01ZX1610E) recruiting patients (pts) receiving treatment for stage IV

gastric cancer. e primary objective of VARIANZ is to investigate resis-

tance factors of HER2 target therapy. Locally assessed HER2 status was

re-assessed centrally using immunohistochemistry (IHC) and in situ hy-

bridization. In 22.2% of all pts HER2 status was not conrmed. Only pts

with conrmed HER2+ status seem to benet from trastuzumab. Here,

we aimed to investigate causes of HER2 discrepancies between local and

central pathologies.

Methods: Information about HER2 test procedures, antibodies for IHC

and participation in round robin tests was collected from participating

pathologies (n=105). Tumor samples with central and local HER2 tests

(n=375) were grouped: central HER2+ concordant to local HER2 status

(HER2+/HER2+) and central HER2- deviating from local HER2 status

(HER2-/HER2+).

Results: Type of antibody used in local pathology and participation in

round robin tests did not inuence HER2 deviation rate. In central

testing, cytoplasmatic HER2 staining of tumor cells was detected in

60.3% of HER2-/HER2+ probes compared to 40.6% in HER2+/HER2+

(p< 0.05, Chi² -test). Concordant to this result the percentage of HER2

membrane stained tumor cells was low in HER2-/HER2+ (13.97 ±

21.87%) vs. HER2+/HER2+ (61.19 ± 31.31%; p< 0.001, Mann-Whitney-

test). 32% of tumor samples originated from surgical resection specimens

in HER2-/HER2+ vs. 9% in HER2+/HER2+ (p< 0.001, Chi² -test). e

majority of pts undergoing surgery received neoadjuvant chemotherapy

(54% of HER2-/HER2+, 66.7% of HER2+/HER2+ pts).

Conclusions: Identication of pts who benet from HER2 targeting ther-

apy remains challenging. e extent of cytoplasmatic HER2 staining and

potential misinterpretation as HER2+ status may inuence test results.

Beyond that, the use of surgical resection specimens for assessment of

HER2 seems to lead to less robust results compared to the use of biopsy

material.

Disclosure Statement: none

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476

Treatment of HER2 Positive Advanced Gastric Cancer:

Deviations in HER2 Results and Its Impact on Survival

Ivonne Haner 1; Katrin Schierle 2; Dieter Maier 3; Birgitta Geier 3;

Elba Raimundez 4, 5; Jan Hasenauer 4, 5; Birgit Luber 6; Albrecht

Kretzschmar 7; Ludwig Fischer von Weikersthal 8; Miriam Ahlborn 9;

Jorge Riera 10; Beate Rau 11; Gabriele Siegler 12; Stefan Fuxius 13;

Thomas Decker 14; Christian Wittekind 2; Florian Lordick 1

1UCCL, Universitätsklinikum Leipzig, Leipzig, Deutschland

2Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

3, Biomax Informatics AG, Planegg, Deutschland

4Hausdor Center for Mathematics - HCM, Universität Bonn, Bonn, Deutschland

5Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg,

Deutschland

6Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische

Universität München, München

7MVZ Mitte, Leipzig, Deutschland

8Praxis für Hämatologie und Internistische Onkologie, Klinikum St. Marien

Amberg, Amberg, Deutschland

9Medizinische Klinik III Hämatologie/Onkologie, Städtisches Klinikum

Braunschweig, Braunschweig , Deutschland

10Klinik für Hämatologie und Onkologie , Universitätsklinikum Marburg ,

Marburg , Deutschland

11Chirurgische Klinik Campus Charité Mitte , Campus Virchow-Klinikum

CCM/CVK, Berlin, Deutschland

12Innere Medizin Onkologie / Hämatologie, Klinikum Nürnberg, Nürnberg,

Deutschland

13Onkologische Schwerpunktpraxis Heidelberg, Heidelberg

14Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,

Deutschland

Purpose: Trastuzumab is the only approved target therapy for HER2 pos-

itive (HER2+) gastric cancer (GC) and used in stage IV 1st line treatment.

Not all treated HER2+ patients respond and most initial responders ex-

perience progression. e resistance mechanisms for trastuzumab in GC

are poorly understood. e aim of the VARIANZ study (NCT02305043,

grant: BMBF 01ZX1610E) was to investigate the biological background of

resistance to HER2 directed target therapy in GC.

Methods: Patients (pts) receiving medical treatment for stage IV GC were

recruited in 34 German sites and followed up to 48 months. HER2 sta-

tus was veried centrally using immunohistochemistry and chromogen-

ic-in-situ hybridization. In addition, HER2 gene expression was assessed

using qPCR.

Results: 548 pts were enrolled and 521 samples were characterized for

HER2. 89 of 521 samples were found HER2+ in central testing. In 78 sam-

ples the locally assessed HER2+ status could not be centrally conrmed.

e deviation rate between local and central testing was 22.2%. In con-

rmed HER2+ GC more tumor cells stained positive for HER2 (61.19

± 31.31% [SD] vs. 13.97 ± 21.87% [SD]; p< 0.001) and a higher HER2/

CEP17 amplication was found (7.31 ± 5.58 [SD] vs. 1.78 ± 0.80 [SD];

p< 0.001). Furthermore, HER2 gene expression (∆Ct) was signicantly

higher in conrmed HER2+ GC (41.83 ± 1.63 [SD] vs. 39.05 ± 1.78 [SD];

p< 0.001).

Pts with a conrmed HER2+ status had a signicantly longer overall sur-

vival when treated with trastuzumab plus chemotherapy (18.6 months

[95%-CI 15.7 - 21.5; n=62] vs. 9.6 months [95%-CI 6.6 – 12.6, n=67], HR

for death 0.45, p< 0.001).

Conclusions: Discrepancies in HER2 assessment in GC between central

pathology and local sites were signicant and mostly found in tumor

specimens with intermediate HER2 levels. Borderline HER2-positivity

and heterogeneity of the marker expression should be considered as a

resistance factor for HER2-directed therapy. HER2-cut-os should be re-

considered and detailed HER2 reports including quantication of stained

tumor cells and HER2 amplication levels might be of value.

535

Somatostatin and Chemokine CXCR4 Receptor Expression

in Pancreatic Adenocarcinoma Relative to Pancreatic

Neuroendocrine Tumours

Ylberta Kajtazi 1; Daniel Kämmerer 2; Jörg Sänger 3; Stefan Schulz 1;

Amelie Lupp 1

1Institute of Pharmacology and Toxicology, Jena University Hospital, Jena,

Deutschland

2Department of General and Visceral Surgery, Zentralklinik Bad Berka,

Bad Berka, Deutschland

3Laboratory of Pathology and Cytology, Zentralklinik Bad Berka, Bad Berka,

Deutschland

Purpose: Pancreatic adenocarcinoma (PAC) represents one of the most

devastating types of cancer with an exceptionally poor prognosis. ere-

fore, improved diagnostic and treatment approaches are urgently need-

ed. An over-expression of somatostatin receptors (SST) as well as of the

chemokine receptor CXCR4 has been shown for many tumor entities. Re-

spective expression data for PAC, however, are scarce and contradictory.

Methods: Overall, 137 tumor samples from 70 patients, 26 of whom

were diagnosed with PAC and 44 with pancreatic neuroendocrine tumor

(PanNET), were compared in terms of SST and CXCR4 expression by im-

munohistochemical analysis using well-characterized rabbit monoclonal

antibodies.

Results: In PAC tumors, only SST1 and CXCR4 expression was detect-

able. SST1 was present in 42.3% and CXCR4 in 7.7% of the cases. e

overall staining intensity, however, was very weak. In contrast to the

tumor cells, in many PAC cases, tumor capillaries showed strong SST3,

SST5 or CXCR4 expression. In PanNETs, SST2 was the most-prominent-

ly expressed receptor. It was observed in 75.0% of the tumors at medi-

um-strong intensity. SST5, SST1 and CXCR4 expression was detected in

20.5%, 15.9% and 11.4% of PanNET cases, respectively, but the staining

intensity for these receptors was only weak. SST2 positivity in PanNET,

but not in PAC, was associated with favorable patient outcomes.

Conclusions: In contrast to PanNET, SST or CXCR4 expression in PAC

is clearly of no therapeutic relevance. However, indirect targeting of these

tumors via SST3, SST5 or CXCR4 on tumor microvessels may represent a

promising additional therapeutic strategy.

Disclosure Statement: Daniel Kaemmerer received funding and support for travel

to meetings from IPSEN and PFIZER. All other authors have nothing to declare.

646

Periampullary Cancer - Survival Among Patients

with Resistant Bacteribilia

Sebastian Homann; Andreas Luu; Orlin Belyaev; Waldemar Uhl

Department of Surgery, St. Josef Hospital Bochum, Ruhr University Bochum,

Bochum, Deutschland

Purpose: In pancreatic surgery preoperative biliary drainage is associated

with bacteribilia, which is more and more frequently caused by resistant

microorganisms. Resistant microorganisms increase the risk for postsur-

gical complications, which may delay recovery and adjuvant therapy. e

question if resistant microorganisms also reduce long term survival is not

answered, yet.

Methods: We performed a prospective survival analysis among all pa-

tients with periampullary cancer who underwent pancreatic head resec-

tion or biliary bypass surgery at St. Josef Hospital, Ruhr University Bo-

chum, from January 2011 until December 2015. e nal date for survival

evaluation was August 31st 2016. Intraoperative bile duct cultures were

collected among all patients immediately aer bile duct transection.

Results: 430 patients were included. e frequency of bacteribilia was 66

%, bacteribilia with resistant microorganisms was 17 %. In 41 % patients

with resistant microorganisms had undergone preoperative antibiotic

therapy, vs. 20 % in patients without resistant microorganisms (p<0.001).

ere were signicantly more postsurgical infectious complications (33 %

vs. 17 %; p=0.003), wound infections (10 % vs. 3 %; p=0.019) and sepsis

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(7 % vs. 2 %; p=0.049) among patients with resistant microorganisms. e

overall survival was 35 % for patients with resistant microorganisms, vs.

51 % for patients without resistant microorganisms (p=0.024). Aer pal-

liative bypass surgery the 3 year survival rate was 25 % for patients with

resistant microorganisms, vs. 34 % for patients without resistant micro-

organisms (p=0.540). Aer R0 resection the 3 year survival rate was 33%

for patients with resistant microorganisms, vs. 62 % for patients without

resistant microorganisms (p=0.055).

Conclusions: Bacteribilia with resistant microorganisms is associated

with higher risk for postsurgical complications with reduced long term

survival. Strategies to avoid bacteribilia with resistant microorganisms

include avoidance of preoperative biliary drainage and rational use of

antibiotics.

759

Histone Deacetylases Expression and Activity in Esophageal

Adenocarcinoma Cells in Vitro

René Thieme 1; Robert Nowotny 1; Ronja Maly 1; Orestis Lyros 1;

Finn K. Hansen 2; Ines Gockel 1

1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,

Transplantations-, Thorax- und Gefäßchirurgie

2Universität Leipzig, Pharmazeutische/Medizinische Chemie, Institut für

Pharmazie

Purpose: e response of EAC patients to common chemotherapeutic

regimens is relatively low (approx. 50%). Improving the response rate in

cancer patients is challenging and novel therapeutic treatment options are

needed. Histone deacetylases (HDAC), an enzyme class with promising

novel features, are involved the regulation of gene expression aecting the

epigenom.

Methods: e expression of Zn2+-dependent HDACs and the endoge-

nous HDAC activity were characterized in a Berrett’s esophagus in vitro

model, containing cells from squamous epithelium, Barrett’s metaplasia,

dysplasia and EAC. Proliferation assays were carried out in EAC cells to

determine cell response to an experimental, HDAC1-3 specic, HDAC

inhibitor (HDACi) in comparison to vorinostat (pan HDACi). e HDAC

activity, the p21 expression, and the histone H3 acetylation were investi-

gated under HDACi treatment.

Results: All Zn2+-dependent HDACs were expressed by each stage of the

Berrett’s esophagus in vitro model. However, the expression intensity was

variable. Vorinostat showed an inhibition of proliferation in the EAC

cells OE33 and OE19 (IC50 of 1.1µM and 1.8µM), while the experimen-

tal HDACi DDK137 revealed an increased anti proliferative eect (IC50

of 0.4µM and 0.6µM), a higher HDAC activity reduction, and higher in-

crease in H3 acetylation. e p21 mRNA-expression showed a cell line,

time and inhibitor specic increase. e highest increase was determined

in OE33 cells (2.5fold) by DDK137 aer 48h, while no increase in p21 was

measured under vorinostat treatment.

Conclusions: We could show a pharmacological more potent HDACi

than vorinostat in EAC cells in vitro. However, further studies are neces-

sary to evaluate the signicance of HDACi and whether HDACi are able

to increase chemosensitivity in EAC patients.

Disclosure Statement: None.

761

Intratumoral Bacterial Lipopolysaccharide (LPS) Detection

as Negative Predictor of Gemcitabine Ecacy in Advanced

Pancreatic Cancer: Translational Results from the AIO-PK0104

Phase 3 Study

Stefan Böck 1, 2; Michael Guenther 3; Volker Heinemann 1, 2; Stephan Kruger 1;

C. Benedikt Westphalen 1; Michael von Bergwelt-Baildon 1, 2;

Thomas Kirchner 2, 3; Michael Haas 1; Steen Ormanns 3

1Department of Internal Medicine III and Comprehensive Cancer Center,

Ludwig-Maximilians-University of Munich, München, Deutschland

2German Cancer Consortium (DKTK), partner site München, Deutschland

3Institute of Pathology, Ludwig-Maximilians-University of Munich, München,

Deutschland

Purpose: A recent pre-clinical study provided evidence that intratumoral

bacteria may mediate gemcitabine resistance by the expression of a long

isoform of the bacterial enzyme cytidine deaminase. is study was con-

ducted in order to determine whether intratumoral LPS detection by IHC

(as surrogate for gram-negative bacterial colonization) is associated with

outcome in advanced pancreatic ductal adenocarcinoma (PDAC) treated

with gemcitabine and non-gemcitabine containing 1st-line chemotherapy.

Methods: Retrospective analysis of archival tumor tissue from 130 pa-

tients treated within the randomized, crossover phase 3 trial AIO-PK0104

(NCT00440167); validation in a second patient cohort (n=113) from a

prospective biomarker study. e correlation of intratumoral LPS to pro-

gression free survival (PFS) and overall survival (OS) was calculated using

the Kaplan-Meier method. Hazard ratios were estimated by Cox propor-

tional hazards regression.

Results: In 31 out of 130 patient samples (24%) from the AIO-PK0104

study intratumoral LPS was detected; in patients with LPS positive tumors

median OS was estimated with 4.4 months, compared to 7.3 months in

patients with LPS negative tumors (HR 1.732, p=0.010). is dierence

in OS was also detected in the subgroup of patients treated with 1st-line

gemcitabine-based treatment (n=71; HR 2.377, p=0.002), whereas no

dierence in OS was observed in the non-gemcitabine subgroup (n=59;

HR 1.275, p=0.478). Within the validation cohort, the LPS positivity rate

was 23% (26 out of 113 patient samples) and LPS detection equally cor-

related with impaired OS in the gemcitabine-based treatment subgroup

(n= 94; HR 1.993, p=0.008) whereas no dierence in OS was observed in

the smaller non-gemcitabine-based treatment subgroup (n=19; HR 2.596,

p=0.219).

Conclusions: e detection of intratumoral bacteria by LPS immunohis-

tochemistry may serve as a negative predictor for gemcitabine ecacy;

this nding indicates a potential role of antibiotic pre-/co-treatment to

overcome bacteria-mediated chemotherapy resistance.

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 67

Inhalt

2018

Index

2018

788

Nivolumab versus Chemotherapy in Advanced Esophageal

Squamous Cell Carcinoma (ESCC): The Phase 3 attraction-3

Study

Peter Thuss-Patience 1; Byoung Chul Cho 2; Ken Kato 3;

Masanobu Takahashi 4; Morihito Okada 5; Chen-Yuan Lin 6; Keisho Chin 7;

Shigenori Kadowaki 8; Myung-Ju Ahn 9; Yasuo Hamamoto 10;

Yuichiro Doki 11; Chueh-Chuan Yen 12; Yutaro Kubota 13; Sung-Bae Kim 14;

Chih-Hung Hsu 15; Eva Holtved 16; Ioannis Xynos 17; Mamoru Kodani 18;

Yuko Kitagawa 19

1Med. Klinik m.S. Hämatologie, Onkologie u. Tumorimmunologie,

Charité – Universitätsmedizin Berlin, Berlin, Deutschland

2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea

3National Cancer Center Hospital Tokyo, Tokio, Japan

4Tohoku University Hospital, Sendai, Japan

5Hiroshima University Hospital, Hiroshima, Japan

6China Medical University Hospital and School of Pharmacy, China Medical

University, Taichung City, Taiwan

7Cancer Institute Hospital Tokyo, Tokio, Japan

8Aichi Cancer Center Hospital, Nagoya, Japan

9Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,

Südkorea

10Keio Cancer Center, School of Medicine, Keio University, Tokio, Japan

11Osaka University Hospital, Osaka, Japan

12Taipei Veterans General Hospital, Taipei, Taiwan

13Showa University Hospital, Tokio, Japan

14Asan Medical Center, University of Ulsan College of Medicine, Seoul, Südkorea

15National Taiwan University Hospital, Taipei City, Taiwan

16Odense University Hospital, Odense, Dänemark

17Bristol-Myers Squibb, Uxbridge, United Kingdom

18ONO Pharmaceutical Company Ltd., Osaka, Japan

19Keio University School of Medicine, Tokio, Japan

Purpose: We report the nal analysis from the phase 3 ATTRACTION-3

study of the programmed death (PD)-1 inhibitor nivolumab (NIVO)

vs chemotherapy (CT) in patients (pts) with unresectable advanced or

recurrent ESCC refractory or intolerant to 1 prior uoropyrimidine/

platinum-based CT.

Methods: Pts were enrolled regardless of tumor PD-ligand 1 (PD-L1)

expression and randomized 1:1 to either NIVO (240 mg Q2W) or inves-

tigator’s choice of paclitaxel or docetaxel. Primary endpoint was overall

survival (OS).

Results: 419 pts were randomized (NIVO = 210, CT = 209). At a mini-

mum follow-up of 17.6 months (mo), NIVO showed a statistically signif-

icant improvement in OS vs CT (HR for death 0.77 [95% CI 0.62–0.96;

P = 0.02]; median OS [95% CI], 10.9 mo [9.2–13.3] vs 8.4 mo [7.2–9.9]).

e proportion of pts alive at 18 mo was numerically larger with NIVO

(31%) vs CT (21%). HRs for the risk of death favored NIVO over CT

across tumor PD-L1 expression levels (PD-L1 ≥ 1%, HR 0.69 [95% CI

0.51–0.94]; PD-L1 < 1%, HR 0.84 [95% CI 0.62–1.14]). Objective response

rates (95% CI) were 19% (14–26) with NIVO and 22% (15–29) with CT.

Responses (median [95% CI]) were more durable with NIVO (6.9 mo

[5.4–11.1] vs CT (3.9 mo [2.8–4.2]). Median (95% CI) progression-free

survival was 1.7 mo (1.5–2.7) with NIVO and 3.4 mo (3.0–4.2) with CT;

12-mo rates were 12% and 7%, respectively. Fewer treatment-related ad-

verse events (TRAEs) were reported with NIVO (any grade, 66%; grade

3–4, 18%) vs CT (any grade, 95%; grade 3–4, 63%). NIVO showed signif-

icant overall improvement in quality of life vs CT through on-treatment

week 42 in the EQ-5D visual analog scale (least square mean, 6.9; 95% CI

3.0–10.9; P < 0.001).

Conclusions: NIVO demonstrated superior OS and a favorable safety

prole vs CT in pts with previously treated advanced ESCC, with survival

benet observed regardless of tumor PD-L1 expression. NIVO may rep-

resent a new standard second-line treatment option for pts with advanced

ESCC.

Disclosure Statement: PT-P has been on ad boards and received personal

fees from Lilly, Roche, MSD, BMS, Pzer, and Merck. KK reports serving as a

consultant for ONO Pharmaceutical, Oncolys BioPharma, BeiGene, and MSD

Oncology; and receiving research funding from ONO Pharmaceutical, BeiGene,

MSD Oncology, and Shionogi, outside the submitted work. B-CC reports receiving

honoraria from ONO Pharmaceutical, during the conduct of this study; and stock

ownership of eraCanVac, Inc.; holding patents for Champions Oncology; serv-

ing as a consultant for ONO Pharmaceutical and Bristol-Myers Squibb; receiving

research funding from Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST,

Champions Oncology, Janssen, Yuhan, ONO Pharmaceutical, Dizal Pharma, and

MSD; receiving honoraria from AstraZeneca, Novartis, Bayer, Mogam Institute,

Champions Oncology, Janssen, Yuhan, Dizal Pharma, and MSD; and serving as

a consultant for AstraZeneca, Novartis, Janssen, Yuhan, MSD, Boehringer-Ingel-

heim, Roche, Pzer, Eli Lilly, and Takeda, outside the submitted work. MT reports

receiving research funding from ONO Pharmaceutical, during the conduct of this

study; and serving as a speaker for ONO Pharmaceutical, Bristol-Myers Squibb,

Daiichi Sankyo, and Taiho Pharmaceutical, outside the submitted work. MO

reports serving as speaker for Taiho Pharmaceutical, Chugai Pharma, Covidi-

en, Johnson & Johnson, and Lilly; and receiving research funding from Taiho

Pharmaceutical, Nippon Kayaku, Chugai Pharma, Covidien, Johnson & Johnson,

Daiichi Sankyo, Yakult Honsha, Lilly Japan, Nihon Medi-Physics, Pzer, Mochida

Pharmaceutical Co., Ltd., and Shionogi, outside the submitted work. SK reports

receiving research funding from ONO Pharmaceutical and Bristol Myers-Squibb

during the conduct of this study; and receiving research funding from Lilly Japan,

Taiho Pharmaceutical, and Boehringer Ingelheim; and receiving personal fees

from Chugai Pharma, Merck Serono, Bayer, Eisai, and Yakult Honsha, outside the

submitted work. M-JA reports receiving honoraria from AstraZeneca, Lilly, MSD,

and Takeda; serving as a consultant for Alpha Pharmaceuticals; and serving as an

advisor with AstraZeneca, Roche, Lilly, MSD, and Takeda, outside the submitted

work. YH reports receiving grants from ONO Pharmaceutical and Bristol-My-

ers-Squibb, during the conduct of this study. YD reports receiving personal fees

from ONO Pharmaceutical, during the conduct of this study; and receiving grants

from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, MSD, Daiichi San-

kyo, Yakult Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan,

Eisai, Shionogi, Otsuka Pharmaceutical, Ajinomoto Pharmaceutical, Astellas

Pharma, Tsumura, AstraZeneca, Johnson & Johnson, Nippon Kayaku, Novartis

Pharma, Pzer Japan, CSL Behring, and Nestle; receiving personal fees from Taiho

Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, MSD, Daiichi Sankyo, Yakult

Honsha, Takeda Pharmaceutical, Kaken Pharmaceutical, Abbott Japan, Eisai,

Shionogi, Otsuka Pharmaceutical, Ajinomoto Pharmaceutical, Teijin Pharma,

Sano, Astellas Pharma, Tsumura, AstraZeneca, Asahi Kasei Pharma, Medtronic,

Johnson & Johnson, Olympus, and Intuitive Surgical; and receiving conference

fees from the Japanese Gastric Cancer Association, the Japan Esophageal Society,

and the Japan Surgical Society, outside the submitted work. C-CY reports receiving

research funding from ONO Pharmaceutical, during the conduct of this study; and

receiving honoraria from Lilly, Merck Sharp & Dohme, Amgen, and Eisai; receiv-

ing research funding from Eisai, Eective Pharmaceuticals, and Deciphera Phar-

maceuticals; and holding consulting roles with Lilly and Merck Sharp & Dohme,

outside the submitted work. S-BK reports receiving researching funding from

Novartis, Genzyme, and Dongkook Pharma, outside the submitted work. C-HH

reports receiving honoraria from ONO Pharmaceutical and Bristol Myers-Squibb,

during the conduct of this study; and serving as a consultant for ONO Pharma-

ceutical; receiving research funding from ONO Pharmaceutical; serving in a con-

sulting role for Novartis, Lilly, and MSD; receiving honoraria from Merck Sharp

& Dohme; and receiving research funding for MSD, AstraZeneca, and Genentech,

outside the submitted work. IX reports employment with Bristol-Myers Squibb

and ownership of stock in Bristol Myers-Squibb, outside the submitted work. MK

reports employment with ONO Pharmaceutical and ownership of stock in ONO

Pharmaceutical, outside the submitted work. YK reports receiving honoraria from

ONO Pharmaceutical, during the conduct of this study; and receiving honoraria

from Ethicon, Olympus, Taiho Pharmaceutical, Chugai Pharma, Nippon Kayaku,

and Asahi Kasei; and receiving research funding from Astellas Pharma, Otsuka,

Kyowa Hakko Kirin, Kowa, CSL Behring, Kaken Pharmaceutical, Shionogi, Daiichi

Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Tsumura & Co., Teijin

Pharma, Medtronic, Boehringer Ingelheim, Merck Serono, Novartis, Asahi Kasei,

Kureha, Sano, Sumitomo Dainippon Pharma, Taisho Toyama Pharma, Nippon

Kayaku, Lilly, Pzer Yakult Honsha, GlaxoSmithKline, Medicon, EA Pharma, Ot-

suka, ONO Pharmaceutical, KCI Licensing, Inc., Nihon Pharmaceutical Co., Ltd.,

Mitsubishi Tanabe Pharma Corporation, Eisai Co., Ltd., Bayer Yakuhin, Ltd, Abbot

Japan Co., Ltd., and FUJIFILM Toyama Chemical Co., Ltd., outside the submitted

work. All other authors report no competing interests.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts68

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2018

Index

2018

800

TGFΒ1 and TGFΒ2 Mediated Epithelial-Mesenchymal

Transition in Esophageal Adenocarcinoma Cells

René Thieme; Olga Chemnitzer; Katharina Götzel; Matthias Mehdorn;

Orestis Lyros; Ines Gockel

Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,

Thorax- und Gefäßchirurgie

Purpose: e esophageal adenocarcinoma (EAC) is characterized by an

early lymphogenic dissemination and a poor prognosis. e tumor biol-

ogy and the impact of autocrine, paracrine and endocrine mediators are

involved in these mechanisms. For dissemination, the tumor cells need to

escape the solid tumor and invade into new target structures. is mech-

anism is described as epitheliale-mesenchymal transition (EMT), which

could be initiated by TGF-beta.

Methods: Two proliferation and motility of the esophageal adenocarcino-

ma cell lines (OE33, OE19) were analyzed aer TGF-beta1 and TGF-beta2

treatment. EMT marker gene expressions (e.g. vimentin) were assessed by

qRT-PCR.

Results: TGF-beta2 led to a deceased proliferation rate compared to un-

treated and TGF-beta1 treated cells in OE33 cells. In OE19 cells both,

TGF-beta1 and TGF-beta2 treatment resulted in an increased prolifera-

tion compared to untreated cells. In OE33 cells the motility was aect-

ed by TGF-beta1 only, while in OE19 cells the motility was increased

by TGF-beta1 and TGF-beta2 compared to untreated cells. e vimen-

tin mRNA-expression in OE33 cells was increased by TGF-beta1 and

TGF-beta2 (14.7-fold and 25.9-fold). However TGF-beta1 and TGF-beta2

only led to a moderate increase in the vimentin mRNA-expression (4.0-

fold and 1.8-fold) in OE19 cells.

Conclusions: TGF-beta1 and TGF-beta2 induce EMT and cellular mo-

tility in a cell line specic pattern. e responsible intracellular signaling

cascades addressed by TGF-beta1 and TGF-beta2 and their contribution

for dissemination in EAC patients need to be investigated with full details.

Disclosure Statement: None.

822

POLO: Ecacy and Health-Related Quality of Life (HRQOL)

with Maintenance Olaparib Following First-Line Platinum-

Based Chemotherapy (PBC) in Patients (PTS) with a Germline

BRCA Mutation and Metastatic Pancreatic Cancer (MPC)

Anke C. Reinacher-Schick 1; Hedy L. Kindler 2; Pascal Hammel 3;

Michele Reni 4; Eric Van Cutsem 5; Teresa Macarulla Mercade 6;

Michael J. Hall 7; Joon Oh Park 8; Daniel Hochhauser 9; Do-Youn Oh 10;

Giampaolo Tortora 11; Hana Algül 12; Eileen M. O‘reilly 13;

David Mcguinness 14; Karen Cui 15; Katia Schlienger 16; Gershon Y Locker 15;

Talia Golan 17; Dirk Arnold 18

1St. Josef-Hospital, Ruhr University Bochum, Bochum, Deutschland

2The University of Chicago, Chicago, United States

3Hôpital Beaujon (AP-HP), Clichy, and University Paris VII, Paris, Frankreich

4IRCCS Ospedale, San Raaele Scientic Institute, MIlan, Italien

5University Hospitals Gasthuisberg, Leuven and KU Leuven, Leuven, Belgien

6Vall d‘Hebron Institute of Oncology, Vall d‘Hebron University Hospital,

Barcelona, Spanien

7Fox Chase Cancer Center, Philadelphia, United States

8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,

Südkorea

9University College London Cancer Institute, London, United Kingdom

10Seoul National University Hospital, Seoul, Südkorea

11Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italien

12Dept. of Internal Medicine II, Klinikum rechts der Isar, Technische Universität

München, München, Deutschland

13Memorial Sloan Kettering Cancer Center, New York, United States

14AstraZeneca, Cambridge, United Kingdom

15AstraZeneca, Gaithersburg, United States

16Merck & Co, Kenilworth, United States

17The Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv, Israel

18Asklepios Tumorzentrum Hamburg AK Altona, Hamburg, Deutschland

Purpose: Pancreatic cancer (PC) pts with germline BRCA1 and/or

BRCA2 mutation (gBRCAm) have shown response to PARP inhibitor

olaparib (O) (Kaufmann et al. JCO 2015). HRQoL assessment was a pre-

dened sec. objective.

Methods: POLO is an international, randomized, double-blind, placebo

(P)-controlled trial of pts with gBRCAm and PC who had received ≥16

wks of 1L PBC for metastatic disease without progression. Pts were then

randomized 3:2 to maintenance O tablets (300 mg bid) or P. Treatment

continued until investigator-assessed disease progression or unacceptable

toxicity. Primary endpoint was progression-free survival (PFS) by blind-

ed independent central review (modied RECIST 1.1). HRQoL was sec.

endpoint, assessed using EORTC QLQ-C30 questionnaire at baseline and

every 4 wks until disease progression, discontinuation and 30 days aer

last dose. Scores ranged from 0 to 100; ≥10-point change or dierence

between arms was considered clinically meaningful.

Results: We screened 3315 pts, identied 247 with gBRCAm, randomized

154 (O 92, P 62), and treated 151 (O 90, P 61). Pt characteristics (O/P):

age, median (range) 57 (37–84)/57 (36–75); male, 58%/50%; ECOG per-

formance status 0, 71%/61%. With 104 events, PFS was signicantly im-

proved with O vs P (hazard ratio [HR] 0.53; 95% CI 0.35, 0.82; P=0.0038;

median PFS 7.4 vs 3.8 mo, respectively). At interim overall survival anal-

ysis (46% maturity), HR was 0.91 (95% CI 0.56, 1.46; P=0.68). Grade ≥3

adverse events occurred in 40% of O- and 23% of P-treated pts. HRQoL

was preserved with O, no di. between arms. Additional HRQoL data will

be presented.

Conclusions: Maintenance O provided a statistically signicant and clin-

ically meaningful improvement in PFS in mPC pts with gBRCAm whose

disease had not progressed on PBC. Safety was consistent with the known

prole for O. POLO is the rst Phase III trial to validate a biomarker-driv-

en treatment in PC.

Disclosure Statement: Study was funded by AstraZeneca and is part of an alliance

between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck &

Co., Inc., Kenilworth, NJ, Usa (MSD).

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 69

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2018

Index

2018

854

Long-Term Survival Following Pancreaticoduodenectomy for

Pancreatic Ductal Adenocarcinoma of the Pancreatic Head

Andreas Luu; Chris Braumann; Torsten Herzog; Gregor Brentano;

Waldemar Uhl

Department of Surgery, St. Josef Hospital Bochum, Bochum, Deutschland

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease

most commonly diagnosed at an advanced stage presenting with distant

metastases or being irresectable. erefore, 5-year overall survival is ex-

tremely poor being estimated at 2.5%. Less than 20% of patients present

with a resectable tumor. Pancreaticoduodenectomy (PD) is the treatment

of choice in cases of PDAC located in the pancreatic head.

Methods: All patients suering from PDAC of the pancreatic head who

underwent a PD in the period from 2007 – 2014 underwent a chart re-

view. Follow-up investigations were performed at least 5 years to detect

long-term survival (LTS). Univariate and multivariate analyses were per-

formed to identify factors inuencing LTS.

Results: Of 152 patients in the study period, 33 patients (22%) were iden-

tied as long-term surviving patients, surviving at least 5 years aer PD.

Median age was 65 (42-80). Male to female ratio was 22 (66.7%) / 11

(33.3%).

Median carbohydrate antigen (CA) 19-9 level was 87 U/ml (2 - 1136 U/

ml) in the LTS-group being signicantly lower than in the remaining co-

hort (131 U/ml; 1 – 9897 U/ml; p = 0.012).

Univariate analyses of pathohistological features between the LTS – group

and the non - LTS-group showed signicant dierences in lymph node

invasion (16x [48.5%] vs. 94x [61.9%); p = 0.014), lymph node ratio (p =

0.029), perineural invasion (24 [72.7%] vs. 129 [84.9%] and tumor grade

(p < 0.001).

Multivariate analysis identied CA 19 – 9 levels, lymph node metastasis

and tumor grade as independent factors contributing to LTS.

Conclusions:

Pathohistological features such as low lymph node ratio, minimal to no

perineural invasion or low tumor grade as well as low levels of CA – 19 - 9

have a signicant impact on long-term survival aer PD in PDAC.

Disclosure Statement: e authors declare no conict of interests.

Genito-urinary Cancer, including Prostate Cancer

Best-of-Abstracts-Vorträge

Health-Related Quality of Life in Long-Term Prostate Cancer

Survivors After Nerve-Sparing and Non-Nerve-Sparing

Radical Prostatectomy – Results from The Multiregional

Procas Study

Salome Adam 1; Eva Martin-Diener 2; Bertrand Camey 3;

Celine Egger Hayoz 3; Isabelle Konzelmann 4; Seyed Mohsen Mousavi 5, 6;

Christian Herrmann 5, 6; Sabine Rohrmann 2, 7; Miriam Wanner 7;

Katharina Staehelin 8; Räto Strebel 9; Marco Randazzo 10; Hubert John 10;

Hans-Peter Schmid 11; Volker Arndt 1, 12

1National Institute for Cancer Epidemiology and Registration (NICER), Zürich,

Schweiz

2Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and

Prevention Institute, Zürich, Schweiz

3Fribourg Cancer Registry, Fribourg, Schweiz

4Health Observatory Valais, Valais Cancer Registry, Sion, Schweiz

5Cancer Registry East Switzerland, St. Gallen, Schweiz

6Cancer Registry Graubünden and Glarus, Chur, Schweiz

7Cancer Registry Zurich and Zug, Zurich, Schweiz

8Basel Cancer Registry, Basel, Schweiz

9Department of Urology, Graubünden Cantonal Hospital, Chur, Schweiz

10Department of Urology, Winterthur Cantonal Hospital, Winterthur, Schweiz

11Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Schweiz

12Unit of Cancer Survivorship, German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

Purpose: Nerve-sparing (NS) surgery was developed to improve postop-

erative sexual and potentially urological outcomes aer radical prostatec-

tomy (RP). However, it is largely unknown how NSRP aects health-re-

lated quality of life (HRQoL) including urinary and sexual outcomes in

prostate cancer (PC) survivors 5-10 years aer diagnosis in comparison

to Non-NSRP.

Methods: e study population included 382 stage pT2-T3N0M0 PC sur-

vivors 5-10 years post-diagnosis, who were identied from the multire-

gional Prostate Cancer Survivorship in Switzerland (PROCAS) study. Brief-

ly, in 2017/2018, PC survivors were identied via six population-based

cancer registries based in both German- and French-speaking Switzer-

land. HRQoL and PC-specic symptom burden was assessed using the

EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Dierences in

HRQoL outcomes between survivors treated with NSRP (uni- & bilateral)

and Non-NSRP were analysed with multivariable linear regression adjust-

ed for age, years since diagnosis, cancer stage, comorbidities at diagnosis

and further therapies, if appropriate. Multiple imputation was performed

to minimize the bias due to missing data.

Results: 5-10 years aer diagnosis, PC survivors treated with NSRP and

Non-NSRP reported similar symptom burden and comparable HRQoL

function scores. e only signicant dierences were reported for sexual

activity, whereas PC survivors who underwent NSRP reported statistical-

ly signicant (p=0.031) higher sexual activity than those on Non-NSRP.

NSRP and Non-NSRP reported similar scores for urinary symptoms and

all other HRQoL outcomes.

Conclusions: NSRP and Non-NSRP were generally associated with com-

parable long-term HRQoL outcomes, but NSRP was linked with signi-

cantly higher sexual activity scores than Non-NSRP. Our results support

nerve-sparing techniques as an option to improve post-operative sexual

but not urinary outcomes aer RP in long-term PC survivors.

Disclosure Statement: e authors have nothing to disclose.

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts70

Inhalt

2018

Index

2018

383

Immune Cell Gene Expression Signature is Associated with

Improved Outcome in Muscle-Invasive Urothelial Bladder

Cancer Patients Treated with Radical Cystectomy

Markus Eckstein 2; Pamela Strissel 3; Reiner Strick 3; Veronika Weyerer 2;

Ralph M. Wirtz 4; Carolin Pfannstiel 2; Adrian Wullweber 2; Fabienne Lange 2;

Philipp Erben 5; Robert Stöhr 2; Simone Bertz 2; Carol I. Geppert 2;

Nicole Furich 2; Helge Taubert 1; Sven Wach 1; Johannes Breyer 6;

Wolfgang Otto 6; Maximilian Burger 6; Christian Bolenz 7; Bastian Keck 1;

Bernd Wullich 1; Arndt Hartmann 2; Danijel Sikic 1

1Department of Urology and Pediatric Urology, University Hospital Erlangen,

Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

2Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-

Universität Erlangen-Nürnberg, Erlangen, Germany

3Department of Gynecology and Obstetrics, University Hospital Erlangen,

Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

4STRATIFYER Molecular Pathology GmbH, Cologne, Germany

5Department of Urology, Medical Faculty Mannheim, Heidelberg University,

Mannheim, Germany

6Department of Urology, University of Regensburg, Regensburg, Germany

7Department of Urology and Pediatric Urology, University Hospital Ulm,

University of Ulm, Ulm, Germany

Purpose: Recently, distinct immune phenotypes in muscle-invasive blad-

der cancer (MIBC) correlating with improved outcome were dened. is

study was conducted to develop a diagnostic assay to assess the immune

status of MIBC and to predict patient outcome aer curative treatment.

Methods: Gene expression of CD3Z, CD8A and CXCL9, dierent im-

mune cell (IC) populations including stromal tumor inltrating lympho-

cytes (sTILs), T-cells, NK-cells, macrophages and PD-1+ IC, and intrinsic

subtypes (MDACC-approach) were assessed in a cohort of 187 curatively

treated MIBC patients (CCC-EMN-cohort). A gene expression signa-

ture was derived by hierarchical-clustering and further validated in the

TCGA-cohort. IC populations in the TCGA cohort were assessed via

CIBERSORT. Benet of platinum-containing adjuvant chemotherapy was

assessed in a pooled cohort of 125 patients.

Results: e gene expression signature of CXCL9, CD3Z and CD8A cor-

relates with quantitative amounts of specic IC populations and sTILs

(CCC-EMN: ρ-range: 0.44-0.74; TCGA: ρ-range: 0.56-0.82) and allows

stratication of three dierent inammation levels in both cohorts (In-

amed high, Inamed low, Uninamed). Highly inamed tumors are

preferentially of basal dierentiation and show favorable 5-year survival

rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Un-

inamed tumors are predominantly of luminal dierentiation and low

5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inamed

tumors exhibit higher levels of targetable immune checkpoints PD-1 and

PD-L1. Patients undergoing adjuvant platinum-based chemotherapy with

“inamed high” tumors showed a favorable 5-year survival rate of 64%

(HR=0.27; merged CCC-EMN and TCGA cohort).

Conclusions: e gene expression signature of CD3Z, CD8A and CXCL9

is reliable to assess the immune status of MIBC and to stratify the sur-

vival of MIBC patients undergoing curative treatment and adjuvant plat-

inum-based chemotherapy. It identies tumors with high expression of

immune checkpoints which are targetable by immunotherapy.

763

The Pure High-Grade Papillary Urothelial Carcinoma of the

Urinary Bladder: A Luminal Lesion Characterized by Frequent

Alterations in Genes Encoding Chromatin-Modifying Proteins

Tician Schnitzler 1; Nadina Ortiz-Brüchle 1; Ursula Schneider 1;

Isabella Lurje 1; Karolina Guricova 1; Alexander Buchner 2; Nadine T. Gaisa 1;

Ruth Knüchel 1; Stefan Garczyk 1

1Pathologie, Uniklinik RWTH Aachen, Aachen, Deutschland

2Urologische Klinik, Klinikum der LMU München , München, Deutschland

Purpose: Non-muscle-invasive bladder cancer is characterized insu-

ciently. It is accepted that high-grade papillary tumors (pTaHG) develop

from a precedent low-grade (LG) lesion. Based on clinical data it is hy-

pothesized that pTaHG tumors might also develop de novo. In this study

we aimed to characterize potentially de novo pTaHG cancers by immuno-

histochemistry (IHC) and NGS, especially focussing on potential targeted

therapies.

Methods: 78 samples from 48 patients presenting with pTaHG cancer

without a history of previous or concomitant pTaLG or muscle-invasive

disease (44 pTaHG, 34 papillary pT1a/pT1HG samples) were analyzed for

protein expression of luminal and basal markers. e presence of genetic

alterations with therapeutic potential was studied by targeted sequencing

in a cohort of 23 samples from 23 patients (19 pTaHG/papillary pT1HG

tumors, four smooth muscle controls). For analysis only the exophytic tu-

mor area was considered.

Results: Potential de novo pTaHG/papillary pT1a/pT1HG tumors were

characterized by a luminal IHC-based phenotype (KRT20+: 74% (58/78),

GATA3+: 99% (77/78), ERbeta+: 96% (75/78), HER2 Dako score 3+: 28%

(22/78)), while lacking in basal marker expression in the majority of cas-

es (KRT5/6+: 3% (2/78), KRT14+: 9% (7/78)). At least one alteration in

genes potentially impacting the selection of targeted therapies, including

frequent alterations in genes encoding chromatin-modifying proteins

(e.g. KDM6A in 47%, ARID1A in 37% of cases), was detected in 95%

(18/19) of cases. Noteworthy, TP53 (21%) and FGFR3 (16%) mutational

rates were similar.

Conclusions: Potential de novo pTaHG tumors are luminal lesions char-

acterized by frequent alterations in genes encoding chromatin-modify-

ing proteins and a similar rate of TP53 and FGFR3 alterations. e vast

majority of cases harbored alterations in genes potentially impacting the

selection of targeted therapies.

Reference:

1. Pathologe (2019) 40(Suppl 2): 41. https://doi.org/10.1007/s00292-019-0616-1

Disclosure Statement: All contributing authors have no conicts of interest to

declare.

Vorträge

132

Checkmate 214 Post Hoc Analyses of Nivolumab Plus

Ipilimumab or Sunitinib in IMDC Intermediate/Poor-Risk

Patients with Previously Untreated Advanced Renal Cell

Carcinoma (ARCC) with Sarcomatoid Features (SRCC)

Marc-Oliver Grimm 1; David F. Mcdermott 2; Toni K. Choueiri 3;

Robert J. Motzer 4; Osvaldo Arén Frontera 5; Saby George 6;

Thomas Powles 7; Frede Donskov 8; Michael R. Harrison 9;

Jerónimo Rodríguez-Cid 10; Yuko Ishii 11; Brent Mchenry 11;

Brian I. Rini 12; Nizar M. Tannir 13

1University Hospital of Jena, Jena, Deutschland

2Beth Israel Deaconness Medical Center, Dana-Farber/Harvard Cancer Center,

Boston, MA, United States

3Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard

Medical School, Boston, MA, United States

4Memorial Sloan Kettering Cancer Center, New York, NY, United States

5Centro de Investigación Clínica Bradford Hill, Recoleta, Chile

6Roswell Park Cancer Institute, Bualo, NY, United States

7Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust,

London, United Kingdom

8Aarhus University Hospital, Aarhus, Dänemark

9Duke Cancer Institute, Durham, NC, United States

10Centro Oncológico, Hospital Medica Sur, Mexico City Area, Mexico

11Bristol-Myers Squibb, Princeton, NJ, United States

12Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, United States

13University of Texas MD Anderson Cancer Center, Houston, TX, United States

Purpose: Patients (pts) with aRCC with sRCC have poor prognosis and

suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus

ipilimumab (N+I) demonstrated superior objective response rate (ORR)

and overall survival (OS) vs sunitinib (S) in previously untreated pts with

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2018

IMDC intermediate/poor (I/P)-risk, clear cell, advanced RCC in the

phase 3 CheckMate 214 trial.

Methods: We performed a post hoc exploratory analysis of N+I vs S in

CheckMate 214 sRCC pts. e presence of sarcomatoid features was as-

sessed by keyword search for “sarcomatoid” in pts with available local pa-

thology reports accompanying pretreatment tumor samples.

Results: 842 (77%) of 1096 intention-to-treat pts had local pathology re-

ports available, including 112 randomized pts with I/P-risk sRCC (N+I,

n=60; S, n=52). Baseline characteristics of sRCC pts were balanced be-

tween arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S

arms had baseline tumor PD-L1 expression ≥1%, which was higher than

in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed

at a minimum follow-up of 30 months, conrmed ORR (56.7% [95% CI

43.2–69.4] vs 19.2% [95% CI 9.6–32.5]; P<0.001) and complete response

rate per investigator (RECIST v1.1; 18.3% vs 0%), OS (median [95% CI]

31.2 [23.0‒not estimable] vs 13.6 [7.7‒20.9] months; HR [95% CI], 0.55

[0.33‒0.90]; P<0.0155 ), and progression-free survival (median [95% CI]

8.4 [5.2–24.0] vs 4.9 [4.0‒7.0] months; HR [95% CI], 0.61 [0.38‒0.97];

P<0.03) per investigator were improved with N+I vs S in I/P-risk pts with

sRCC. No new safety signals were seen in sRCC pts.

Conclusions: In this post hoc descriptive subgroup analysis of Check-

Mate 214, N+I demonstrated promising ecacy and prolonged survival

vs S, with consistent safety, in untreated, I/P-risk, advanced clear cell RCC

with sarcomatoid features. Prospective studies of N+I that include pts

with sRCC are ongoing.

372

Apalutamide (APA) and Overall Survival (OS) in Patients (PTS)

with Nonmetastatic Castration-Resistant Prostate Cancer

(NMCRPC): Updated Results from The Phase 3 Spartan Study

Boris A. Hadaschik 1; Matthew R. Smith 2; Fred Saad 3; Simon Chowdhury 4;

Stéphane Oudard 5; Julie N. Gra 6; David Olmos 7; Paul N. Mainwaring 8;

Ji Youl Lee 9; Hiroji Uemura 10; Peter De Porre 11; Andressa Smith 12;

Ke Zhang 13; Angela Lopez-Gitlitz 14; Eric J. Small 15

1University of Duisburg-Essen, Essen, and Ruprecht-Karls University Heidelberg,

Heidelberg, Germany

2Massachusetts General Hospital Cancer Center and Harvard Medical School,

Boston, MA, USA

3Centre Hospitalier de l’Université de Montréal, Université de Montréal,

Montréal, Québec, Canada

4Guy’s, King’s and St. Thomas’ Hospitals, and Sarah Cannon Research Institute,

London, UK

5Georges Pompidou Hospital, Paris, France

6VA Portland Health Care System, Portland and Knight Cancer Institute, Oregon

Health & Science University, Portland, OR, USA

7Spanish National Cancer Research Centre (CNIO), Madrid and Hospitales

Universitarios Virgen de la Victoria y Regional de Málaga, Spain

8Centre for Personalized Nanomedicine, University of Queensland, Brisbane,

Australia

9St. Mary’s Hospital of Catholic University, Seoul, South Korea

10Yokohama City University Medical Center, Yokohama, Japan

11Janssen Research & Development, Beerse, Belgium

12Janssen Research & Development, Spring House, PA, USA

13Janssen Research & Development, San Diego, CA, USA

14Janssen Research & Development, Los Angeles, CA, USA

15Helen Diller Family Comprehensive Cancer Center, University of California

San Francisco, San Francisco, CA, USA

Purpose: In the Ph3 PBO-contr. SPARTAN study, APA with ongoing

ADT signi. improved metastasis-free survival (MFS) (HR, 0.28; 95% CI,

0.23-0.35; p < 0.001), time to symptomatic progress., and progress.-free

survival on 2nd therapy compared with PBO with ongoing ADT in pts with

nmCRPC. At the primary analysis for MFS, APA was associa. with im-

proved OS (HR, 0.70; 95% CI, 0.47-1.04; p = 0.07) and time to initiation of

cytotoxic chemotherapy. OS results were immature, with only 104 of 427

events (24%) required for the prespecied nal OS analysis. We report a

second interim analysis (IA2) for OS aer 285 events (65% of required

events).

Methods: Pts with nmCRPC and PSA doubling time of ≤ 10 mths were

random. 2:1 to APA (240 mg QD) or PBO, with ongoing ADT. e OS

eect of APA vs PBO was assessed using a group sequential testing pro-

cedure with O’Brien-Fleming-type alpha spending function. e required

p value for stati. signi. at IA2 was 0.0121. OS was analyzed by Kaplan-

Meier method and Cox model.

Results: At 41 mths’ med. follow-up and 285 OS events, APA was asso-

cia. w/ improved OS compared with PBO (HR, 0.75; 95% CI, 0.59-0.96;

p = 0.0197). e 4-yr OS rates for APA and PBO were 72.1% and 64.7%,

respect.. Aer unblinding the study and prior to IA2, 76 nonprogressing

PBO pts (19%) crossed over to open-label APA. At IA2, the proportion of

pts who received subsequent life-prolonging therapy was 68% in the PBO

group and 38% in the APA group. Rates of disconti. due to progressive

disease and AE were 34% and 14%, for the APA group, and 74% and 8%

for the PBO group. Rates of treatment-emergent AEs for APA at IA2 were

similar to the rates previously reported at IA1.

Conclusions: At IA2, APA was associa. w/ a 25% reduc. in risk of death

compared with PBO. is OS benet for APA was observed desp. cross-

over of PBO pts to APA and higher rates of subsequent life-prolonging

therapy for PBO pts. APA safety prole remained unchanged. ese re-

sults further support APA as a standard of care option for pts with high-

risk nmCRPC.

Reference:

1. ESMO Congress Barcelona 27 Sep-01 Oct 2019

690

Profound: Phase III Study of the Ecacy and Safety of

Olaparib versus Enzalutamide or Abiraterone Acetate in

Men with Metastatic Castration-Resistant Prostate Cancer

(mCRPC) and Homologous Recombination Repair Gene (HRR)

Alterations

S Feyerabend 1; M Hussain 2; J Mateo 3; K Fizazi 4; F Saad 5; N Shore 6;

SSandhu 7; K Chi 8; O Sartor 9; N Agarwal 10; D Olmos 11; A Thiery-Vuillemin 12;

P Twardowski 13; N Mehra 14; C Goessl 15; J Kang 15; J Burgents 16; W Wu 15;

AKohlmann 17; C Adelman 17; J De Bono 18

1Studienpraxis Urologie, Nürtingen, Deutschland

2Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Feinberg School of Medicine, Chicago, United States

3Vall d’Hebron Institute of Oncology, Barcelona, Spanien

4Institut Gustave Roussy, University of Paris Sud, Villejuif, Frankreich

5Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, Kanada

6Carolina Urologic Research Center, Myrtle Beach, United States

7Peter MacCallum Cancer Centre, Melbourne, Australien

8BC Cancer Agency, Vancouver, Kanada

9Tulane University School of Medicine, New Orleans, United States

10Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City,

United States

11Spanish National Cancer Research Centre (CNIO), Hospitales Universitarios

Virgen de la Victoria y Regional de Málaga, Madrid, Spanien

12CU-PH Medical Oncology Unit, CHU Besançon, Besançon, Frankreich

13City of Hope National Medical Center, Duarte, United Kingdom

14Radboud University Medical Center, Nijmegen, Netherlands Antilles

15AstraZeneca, Gaithersburg, United States

16Merck & Co., Inc, Kenilworth, United States

17AstraZeneca, Cambridge, United Kingdom

18The Institute of Cancer Research and Royal Marsden, London, United Kingdom

Purpose: mCRPC is a molecularly heterogenous disease. Tumors in a

sizable proportion of patients with mCRPC harbor loss-of-function al-

terations in genes involved in HRR (egBRCA1,BRCA2andATM). HRR

alterations have been associated with increased sensitivity to the PARP in-

hibitor olaparib in mCRPC. e PROfound study (NCT02987543) evalu-

ates olaparib ecacy and safety versus either enzalutamide or abiraterone

acetate, in mCRPC patients with an HRR alteration.

Methods: PROfound is a randomized, open-label, Phase III study in

men with mCRPC, for whom prior new hormonal agent treatment for

metastatic prostate cancer and/or CRPC had failed. Eligible patients had

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2018

Index

2018

a qualifying tumor HRRm in 1 of 15 genes, prospectively and centrally

determined in tumor tissue using an investigational next-generation se-

quencing test (Foundation Medicine, Inc.). Two cohorts were enrolled:

Cohort A (n=245) included patients with alterations in BRCA1, BRCA2

or ATM; Cohort B included patients with an alteration in 12 other HRR

genes (n=142). Patients were randomized (2:1) to olaparib tablets (300mg

bid) or physician’s choice of either enzalutamide (160 mg orally od) or

abiraterone acetate (1000 mg orally od + 5 mg bid prednisone). Treatment

continued until radiographic progression (assessed by blinded indepen-

dent central review or lack of treatment tolerability. e primary endpoint

of radiographic progression-free survival (rPFS) in Cohort A was assessed

by BICR using RECIST 1.1 and PCWG3 criteria and analyzed via strati-

ed log-rank test.

Results and conclusions: e abstract will be updated with results and

conclusions pending data availability.

Funding Source: AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of

Merck & Co., Inc., Kenilworth, NJ, USA

Poster

147

Prediction of Response Rate and Long-Term Survival in

Polychemotherapy for Metastatic Penile Cancer by the

Glasgow Prognostic Score

Desiree Louise Dräger; Tim Buchholz; Sophie Groh; Oliver Hakenberg

Urologische Universitätsklinik, Universitätsmedizin Rostock, Rostock,

Deutschland

Purpose: e Glasgow Prognostic Score (GPS) is dened by a combina-

tion of elevated C-reactive protein serum level (> 10 mg/L) and of hypoal-

buminemia (< 35 g/L). It is considered in a variety of tumor entities as an

independent prognostic marker, which predicts the biological behavior of

malignant tumors. e survival rates for metastatic penile carcinoma are

low. ere is increasing evidence that patient-related prognostic factors,

such as a persistent systemic inammatory response, lead to low survival

rates in tumor patients. e aim of the current study was to clarify the

value of GPS in metastatic penile carcinoma in terms of response rate and

long-term survival.

Methods: e correlation of GPS and long-term survival and response

rate was studied in 68 patients with metastatic penile carcinoma. For this

purpose, a score of C-reactive protein and albumin was determined pri-

or to systemic treatment in order to correlate this consecutively with the

follow-up.

Results: e survival and response of GPS-1 patients was signicantly

worse than that of GPS-0 patients (p = 0.006) and the survival and re-

sponse of GPS-2 patients was signicantly worse than that of GPS-1 pa-

tients (p <0.0001). Multivariate analysis showed that GPS (p <0.0001),

tumor stage (p = 0.004), venous and lymph vessel invasion (p = 0.011)

were factors that were independently associated with a worse prognosis.

Conclusions: e GPS can stratify the clinical outcome of penile cancer

and can be used as a prognostic indicator.

Disclosure Statement: none

148

Quantication of Lymphedema of the Lower Extremity and

the External Genitals After Inguinal Lymphadenectomy in

Penile Cancer Patients and Its Impact on the Quality of Life

Desiree Louise Dräger; Eva-Maria Fritz; Julia Nolting; Maria Woehl;

Oliver Hakenberg

Urologische Universitätsklinik, Universitätsmedizin Rostock, Rostock,

Deutschland

Purpose: Lymphedema of the lower extremity and the external genitals as

a result of penile cancer treatment is a chronic disease that can signicant-

ly impair the quality of life. In the present study, various aspects of lymph-

edema associated with penile cancer were examined, including measure-

ment methods, denitions, risk factors and, in particular, the eects on

the physical, psychological and emotional well-being of aected men.

Methods: In a retrospective cohort study, we investigated the relationship

between lymphedema, quality of life and surgical factors (radical vs. mod-

ied lymphadenectomy, LND). A total of 76 men, surgically treated for

penile cancer, were evaluated at least 1 year aer LND.

Results: In 29% of men lymphedema was detected (leg volume dierence

> 200cm³). Aected men have a reduced self-esteem due to a distorted

body image. Negative emotions reported include anxiety, frustration, sad-

ness, anger, anxiety, and reduced self-esteem.

Conclusions: Lymphedema as a result of penile cancer treatment contin-

ues to be a signicant quality of life problem with consequences for phys-

ical, mental and emotional well-being. e development of lymphedema

leads to physical impairment, including impaired function, diminished

strength, fatigue and pain in the aected limb.

Disclosure Statement: none

155

Traumatic Spinal Cord Injury Confers Bladder Cancer Risk:

Lessons from a Comparison of Clinical Data with the National

Database

Ralf Böthig 1; Ines Kurze 2; Kai Fiebag 1; Christian Tiburtius 1; Birgitt Kowald 3;

Sven Hirschfeld 4; Roland Thietje 4; Albert Kaufmann 5; Wolfgang Schöps 6;

Michael Zellner 7; Holger Böhme 8; Thura Kadhum 9; Klaus Golka 9

1BG Klinikum Hamburg, Abt. Neuro-Urologie, Querschnittgelähmten-Zentrum,

Hamburg, Deutschland

2Zentralklinik Bad Berka, Klinik für Paraplegiologie und Neuro-Urologie, Bad

Berka, Deutschland

3BG Klinikum Hamburg, Biomechanisches Labor, Hamburg, Deutschland

4BG Klinikum Hamburg, Querschnittgelähmten-Zentrum, Hamburg,

Deutschland

5Kliniken Maria Hilf GmbH, Zentrum für Kontinenz & Neuro-Urologie,

Mönchengladbach, Deutschland

6Praxis Urologie Sankt Augustin

7Johannesbad Fachklinik, Abt. Urologie und Neuro-Urologie, Bad Füssing,

Deutschland

8Asklepios Klinik Barmbek, Klinik für Urologie, Hamburg, Deutschland

9Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Dortmund,

Deutschland

Purpose: Life expectancy for people with traumatic spinal cord injury

(TSCI) is increasing due to advances in treatment methods and in neu-

ro-urology. us, developing urinary bladder cancer (UBC) is gaining

importance.

Methods: Single-center retrospective evaluation of consecutive in- and

out-patient data with spinal cord injury between January 1, 1998 and De-

cember 31, 2018 was carried out and data were compared with publicly

available UBC data of the German population from the Center for Cancer

Registry Data of the Robert Koch-Institute.

Results: A total of 37 (4 female, 33 male) out of 7004 patients with TSCI

were diagnosed with histologically proven urinary bladder cancer. Medi-

an follow-up of TSCI patients with UBC was 85 months. Median age at

bladder cancer diagnosis was 54.0 years, which is well below the average

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2018

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2018

for bladder cancer cases in the general population in Germany (male: 73,

female: 77 years).

All but two patients had a latency period between the onset of TSCI and

tumour diagnosis of more than 10 years (median: 30.0 years).

Of the 37 patients, 30 (81%) had muscle invasive bladder cancer at ≥T2 at

the time of diagnosis, 27 out of 37 patients showed a histologically poorly

dierentiated G3 carcinoma. Both frequency distributions dier signi-

cantly between TSCI patients (p <0.0001 each) and the normal German

population.

Median survival for all patients was 12.0 months (transitional cell carci-

noma (n=31) 13 months; squamous cell carcinoma (n=5) 4 months, p =

0.0039). e prognosis of the 24 cystectomized patients was 15.0 months

and thus signicantly better than in those without cystectomy (p = 0.0148)

32 patients suered from urodynamically conrmed neurogenic detrusor

overactivity while 5 patients (all male) had detrusor acontractility.

Long-term suprapubic or indwelling catheterization was found in only 8

patients for a total of only 5.09% (median: 15.5 months) of the latency of

all patients.

Conclusions: e results indicate that the neurogenic bladder caused by

traumatic SCI itself is the main risk factor for bladder cancer.

216

Clinical Outcome of PSMA-Guided Radiotherapy for Patients

with Oligorecurrent Prostate Cancer

Katharina Sprute 1; Stefan A. Koerber 2, 3, 4; Clemens Kratochwil 1, 5;

Matthias F. Haefner 2, 3, 4; Henrik Rathke 1; Klaus Herfarth 2, 3, 4, 6; Klaus

Kopka 7, 8; Tim Holland-Letz 9; Uwe Haberkorn 1, 5; Juergen Debus 2, 3, 4, 6, 8, 10;

Frederik L. Giesel 1, 5, 8

1Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg,

Deutschland

2National Center for Tumor diseases (NCT), Heidelberg, Deutschland

3Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland

4Department of Radiation Oncology, Heidelberg University Hospital,

Heidelberg, Deutschland

5Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center

(DKFZ), Heidelberg, Deutschland

6Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation

Oncology, Heidelberg University Hospital, Heidelberg, Deutschland

7Division of Radiopharmaceutical Chemistry, German Cancer Research Center

(DKFZ), Heidelberg, Deutschland

8German Cancer Consortium (DKTK), Heidelberg, Deutschland

9Department of Biostatistics, German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

10Clinical Cooperation Unit Radiation Oncology, German Cancer Research

Center (DKFZ), Heidelberg, Deutschland

Purpose: First line treatment of patients with recurrent, metastatic pros-

tate cancer is a combination of hormone therapy with or without chemo-

therapy/ abiraterone, as a systemic, palliative treatment. A new perspec-

tive is given by PSMA-PET/CT-guided irradiation, which demonstrated

promising ecacy in recent trials. e current study aimed to classify the

type and localization of metastases aer primary treatment and its clinical

outcome.

Methods: Between 2011 and 2019, 86 patients (mean age of 69 years) with

recurrent, oligometastatic prostate cancer received a PSMA-PET/CT fol-

lowed by a precise irradiation of their metastases. 60 patients underwent

a clinical follow-up including a quality of life status. Data were analyzed

retrospectively regarding the region of relapse and the primary endpoints

overall survival (OS), biochemical progression free survival (bPFS) and

androgen deprivation therapy (ADT)-free survival.

Results: e median follow- up was 24 months (range 4-72). According

to the d’Amico risk classication, 90.7% of all patients were categorized as

high-risk. A median amount of 1.0 metastases per patient could be identi-

ed. In total, 49.4% of the metastases were considered as metastases of the

bone, 34.1% were nodal metastases within and 16.5% nodal metastases

outside of the pelvis. A 2-year OS rate of 95.7% and a 2-year bPFS rate

of 85.1% were calculated. e data analysis revealed a mean ADT- free

time of 15.9 months (range 3-40). Biochemical response was detected in

83.3% of the cohort. If a progress monitoring via PSMA-PET/CT was im-

plemented, the standard uptake value (SUV) of the irradiated metastases

was reduced signicantly.

Conclusions: PSMA-guided radiotherapy is a promising, novel therapeu-

tic approach for oligorecurrent prostate carcinoma to extent OS and bPFS

in comparison to systemic therapy and should be more considered in the

recurrent situation. However, prospective, randomized trials are necessary

to conrm and validate the analyzed data with a larger cohort of patients.

295

Clinical Outcomes According to PD-L1 Status and Age in the

Prospective International Saul Study of atezolizumab (ATEZO)

for Locally Advanced or Metastatic Urothelial Carcinoma (UC)

or Non-UC of the Urinary Tract

Friedemann Zengerling 1; Cora N. Sternberg 2; Axel S. Merseburger 3;

Ernest Choy 4; Daniel Castellano 5; Fernando Lopez-Rios 6; Nick James 7;

Giuseppe L. Banna 8; Ugo De Giorgi 9; Cristina Masini 10; Aristotelis

Bamias 11; Xavier Garcia del Muro 12; Thomas Powles 13; Ignacio Duran 14, 15;

Craig Gedye 16; Marija Gamulin 17; Lajos Geczi 18; Sabine de Ducla 19;

Simon Fear 19; Yohann Loriot 20

1Department of Urology, University Hospital Ulm, Ulm, Deutschland

2Weill Cornell Medicine, New York, NY, United States

3Department of Urology, Campus Lübeck, University Hospital Schleswig-

Holstein, Lübeck, Deutschland

4CREATE Centre, Section of Rheumatology, Division of Infection and Immunity,

Cardi University School of Medicine , Cardi, United Kingdom

5Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid,

Spanien

6Hospital Universitario HM Sanchinarro, Madrid, Spanien

7Institute of Cancer and Genomic Services, University of Birmingham, and

Cancer Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom

8Cannizzaro Hospital, Catania, Italien

9Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS,

Meldola, Italien

10Medical Oncology Unit, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italien

11National and Kapodistrian University of Athens, Alexandra Hospital, Athens,

Griechenland

12Institut Catala d’Oncologia, IDIBELL, Barcelona, Spanien

13Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary

University of London, St Bartholomew’s Hospital, London, United Kingdom

14Hospital Universitario Virgen del Rocio, Seville, Spanien

15Hospital Universitario Marques de Valdecilla, Santander, Spanien

16Calvary Mater Newcastle, Waratah, NSW, Australien

17University Hospital Centre ‘Zagreb’, Zagreb, Kroatien

18National Institute of Oncology, Budapest, Ungarn

19F. Homann-La Roche Ltd, Basel, Schweiz

20Department of Cancer Medicine and INSERM U981, Université Paris-Sud,

Université Paris-Saclay, Gustave Roussy, Villejuif, Frankreich

Purpose: Atezo, a monoclonal antibody targeting PD-L1, is an ap-

proved therapy for locally advanced/metastatic UC based on IMvig-

or210 and IMvigor211 phase II and III trials. e single-arm SAUL study

(NCT02928406) with a broader patient (pt) population demonstrated

median overall survival (OS) of 8.7 months and a safety prole consistent

with previous atezo trials.

Methods: Pts with locally advanced/metastatic UC or non-UC of the uri-

nary tract received atezo 1200 mg every 3 weeks until disease progression

or unacceptable toxicity. Populations excluded from IMvigor211 (renal

impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable

controlled autoimmune disease, concomitant steroids, HIV positive, non-

UC) were eligible. e primary endpoint was safety; OS and overall re-

sponse rate (ORR) were secondary endpoints. Predened subgroup anal-

yses included outcomes according to PD-L1 status (VENTANA SP142)

and age in the overall population (and the IMvigor211-like subgroup for

PD-L1).

Results: Between Nov 2016 and Mar 2018, 1004 pts were enrolled; 997

received atezo. Median (95% CI) OS was overall IC 0/1 vs IC 2/3: 7.9 (6.8–

9.1) vs. 11.6 (8.8–18.8); IMvigor211-like IC 0/1 vs 2/3: 9.0 (7.8–10.4) vs

14.5 (9.5–18.8). ORR (95% CI) was overall IC 0/1 vs IC 2/3: 10% (8–13) vs

21% (16–26); IMvigor211-like IC 0/1 vs 2/3: 10% (7–13) vs 23% (17–30).

Treatment response was observed in all age groups (ORR [95% CI], ≥65 y:

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2018

14% [12–17]; ≥75 y: 13% [9–18]; ≥80 y: 8% [3–16]). Incidences of grade

≥3 treatment-related adverse events were similar irrespective of PD-L1

status (overall IC 0/1 vs 2/3: 11% vs 16%; IMvigor211-like IC 0/1 vs 2/3:

11% vs 15%) or age (≥65 y: 13%; ≥75 y: 12%; ≥80 y: 10%).

Conclusions: OS and ORR appear more favorable in IC2/3 vs IC0/1 sub-

groups (overall and in the IMvigor211-like population). Atezo was eec-

tive and well tolerated across subgroups including elderly pts.

Reference:

1. Sternberg et al. ASCO 2019

323

Association Between Depth of Response (DepOR) and

Overall Survival (OS): Exploratory Analysis of Nivolumab +

Ipilimumab (N+I) vs Sunitinib (S) in Patients with Previously

Untreated Advanced Renal Cell Carcinoma (ARCC) in

Checkmate 214

Viktor Gruenwald 1; Toni K. Choueiri 2; Brian I. Rini 3; Thomas Powles 4;

Saby George 5; Marc-Oliver Grimm 6; M. Brent Mchenry 7;

Matthew Maurer 7; Robert J. Motzer 8; Hans J. Hammers 9; Nizar M. Tannir 10;

Laurence Albiges 11

1Interdisciplinary Genitourinary Oncology at the West-German Cancer Center,

Clinic for Internal Medicine (tumor research) and Clinic for Urology, University

Hospital Essen, Essen, Deutschland

2Department of Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham

and Women’s Hospital, and Harvard Medical School, Boston, United States

3Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer

Institute, Cleveland, United States

4Department of Medicine, Barts Cancer Institute, Queen Mary University of

London, Royal Free NHS Trust, London, United Kingdom

5Department of Medicine, Roswell Park Cancer Institute, Bualo, United States

6Department of Urology, Jena University Hospital, Jena, Deutschland

7Bristol-Myers Squibb, Princeton, United States

8Department of Medicine, Memorial Sloan Kettering Cancer Center, New York,

United States

9Department of Medicine, UT Southwestern – Kidney Cancer Program, Dallas,

United States

10Department of Genitourinary Medical Oncology, University of Texas MD

Anderson Cancer Center, Houston, United States

11Department of Medical Oncology, Gustave Roussy, Villejuif, Frankreich

Purpose: DepOR (max % reduction from baseline in sum of target lesion

diameters) has shown prognostic value for long-term survival in multiple

malignancies. Among aRCC intention-to-treat patients (pts) in Check-

Mate 214 superior ecacy was recently shown with N+I over S at 30-mo

min follow-up. e relationship between DepOR and OS was evaluated in

CheckMate 214 to determine a potential DepOR threshold predictive of

long-term OS with N+I.

Methods: Pts were randomized 1:1 to N+I (3 mg/kg + 1 mg/kg IV) Q3W

for 4 doses, followed by N (3 mg/kg IV) Q2W, or S 50 mg/day orally for

4 wk (6-wk cycles). An exploratory analysis of OS by DepOR quartiles

was conducted (Q0, no reduction; Q1, >0–≤25%; Q2, >25–≤50%; Q3,

>50–≤75%; Q4, >75–≤100%).

Results: Of 550 and 546 pts randomized to N+I or S, 479 and 459, re-

spectively, had postbaseline target lesion measurements. Among Q0 pts,

median OS was longer and OS probabilities were notably higher with N+I

vs S. Overall, greater DepOR was associated with improved OS in both

arms. e OS probability HR (95% CI) vs Q0 was 0.63 (0.43–0.93) for Q1,

0.65 (0.42–1.01) for Q2, 0.22 (0.13–0.38) for Q3, and 0.18 (0.11–0.32) in

the N+I arm (all P<0.0001). e OS probability vs Q0 progressively de-

creased with greater DepOR in arm S; however, N+I pts with >50–≤75%

(Q3) tumor reduction had similar OS benets as those with >75% (Q4)

reduction, whereas only Q4 pts achieved comparable OS with S (203/550

[37%] N+I vs 46/546 [8%] S randomized pts). Receiver operating charac-

teristic analysis supported a >50% DepOR threshold for greatest OS bene-

t with N+I. Additional analyses of the relationship between DepOR and

outcomes across arms will be presented.

Conclusions: e relationships between DepOR and OS are distinct for

N+I vs S, with a greater percentage of N+I pts having prolonged OS. Sim-

ilar notable OS benets in N+I DepOR Q3 and Q4 suggest that a DepOR

threshold >50% may be a useful indicator of potential for long-term sur-

vival with N+I in aRCC pts. Prospective analyses to determine clinical

applications are needed. Previously presented at Esmo 2019, Fpn 950P,

Grünwald et al. Reused with permission.

Disclosure Statements:

Viktor Grünwald reports grants and personal fees from Pzer; grants, personal

fees and non-nancial support from Bristol-Myers Squibb; personal fees and

non-nancial support from Roche; personal fees and non-nancial support from

Novartis; personal fees and non-nancial support from EISAI; grants, personal

fees, and non-nancial support from Ipsen; and grants and personal fees from

EUSA Pharm, during the conduct of the study and grants, personal fees, non--

nancial support, and stock ownership from MSD; grants from Novartis; grants,

personal fees, and stock ownership from AstraZeneca; grants, personal fees,

non-nancial support, and stock ownership from Bristol-Myers Squibb; personal

fees and non-nancial support from Merck Serono; personal fees from Roche;

personal fees from Pzer; personal fees from Lilly; personal fees and non-nancial

support from PharmaMar; personal fees from Nanobiotix; and personal fees from

Janssen, outside the submitted work.

Toni K. Choueiri reports research funding (institutional and personal) from

AstraZeneca, Alexion, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC,

Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, Tracon, Genentech,

Roche, Roche Products Limited, F. Homann-La Roche, GlaxoSmithKline, Lilly,

Merck, Novartis, Peloton, Pzer, Prometheus Labs, Corvus, Calithera, Analysis

Group, Sano/Aventis, and Takeda; honoraria from AstraZeneca, Alexion, Sano/

Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai,

Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited,

F. Homann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pzer, EMD

Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, National Comprehensive

Cancer Network, Analysis Group, Michael J. Hennessy (MJH) Associates, Inc

(healthcare communications company with several brands such as OnClive, Peer-

View and PER), L-path, Kidney Cancer Journal, Clinical Care Options, Platform

Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology,

New England Journal of Medicine, Lancet Oncology, Heron erapeutics, and

Lilly; consulting or advisory role with AstraZeneca, Alexion, Sano/Aventis, Bayer,

Bristol-Myers Squibb/ER Squibb and Sons LLC, Cerulean, Eisai, Foundation

Medicine Inc., Exelixis, Genentech, Heron erapeutics, Lilly, Roche, GlaxoSmith-

Kline, Merck, Novartis, Peloton, Pzer, Emd Serono, Prometheus Labs, Corvus,

Ipsen, Up-to-Date, National Comprehensive Cancer Network, and Analysis Group;

patents, royalties or other intellectual properties: International Patent Application

No. PCT/US2018/12209, titled “PBRM1 Biomarkers Predictive of Anti-Immune

Checkpoint Response,” led January 3, 2018, claiming priority to U.S. Provisional

Patent Application No. 62/445,094, led January 11, 2017, and International Patent

Application No. Pct/US2018/058430, titled “Biomarkers of Clinical Response and

Benet to Immune Checkpoint Inhibitor erapy,” led October 31, 2018, claim-

ing priority to U.S. Provisional Patent Application No. 62/581,175, led November

3, 2017.

Brian I. Rini reports research funding to institution from Pzer, Merck, GNE/

Roche, Peloton, Aveo, AstraZeneca, and Bristol-Myers Squibb; consulting fees

from Bristol-Myers Squibb, Pzer, GNE/Roche, Aveo, Novartis, Synthorx,

Peloton, Compugen, Merck, Corvus, and Exelixis; and stock holding with PTC

erapeutics.

omas Powles reports research funding from AstraZeneca/MedImmune and

Roche/Genentech; consulting/advisory roles with Genentech/Roche, Bristol-Myers

Squibb, Merck, Novartis, and AstraZeneca; honoraria from Roche/Genentech,

Bristol-Myers Squibb, and Merck; and other relationships with Ipsen and Bristol-

Myers Squibb.

Saby George reports consulting/advisory roles with Bayer, Bristol-Myers Squibb,

Novartis, Exelixis, Janssen, Corvus, Genentech, Sano/Genzyme, Pzer, and EMD

Serono; and grants from Acceleron, Merck, Agensys, and Eisai.

Marc-Oliver Grimm reports research funding and consulting/advisory fees

from Novartis; research funding, consulting/advisory fees, and honoraria from

Bristol-Myers Squibb; consulting/advisory fees and honoraria from Pzer, Bayer

HealthCare, Sano Aventis, AstraZeneca, MSD, Janssen Cilag, and ONO Pharma-

ceutical; honoraria from Astellas, Hexal, Apohepha, Ipsen Pharma, and Medac;

consulting/advisory fees from Intuitive Surgical and Amgen, outside the submitted

work.

M. Brent McHenry reports employment with and stock ownership in Bristol-

Myers Squibb.

Matthew Maurer reports employment with and stock ownership in Bristol-Myers

Squibb.

Robert J. Motzer reports research funding paid to institution from Bristol-Myers

Squibb, Pzer, Novartis, Eisai, Exelixis, and Genentech/Roche; and consultancy

roles with Bristol-Myers Squibb, Pzer, Novartis, Eisai, Exelixis, Genentech/Roche,

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Merck, Incyte, and Lilly.

Hans J. Hammers reports clinical trial support and advisory board roles with

Bristol-Myers Squibb and Merck; and advisory board roles with Pzer, Exelixis,

Armo Biosciences, and Novartis.

Nizar M. Tannir reports research funding and advisory board roles with Bris-

tol-Myers Squibb, Pzer, Novartis, and Exelixis Inc; research funding from Cali-

thera Bioscience; advisory board roles with Nektar erapeutics, Oncorena, and

Eisai Medical Research; and a speakers bureau role with ONO Pharmaceutical.

Laurence Albiges reports consulting (by institution) for Pzer, Novartis,

Bristol-Myers Squibb, Ipsen, Roche, MSD, and AstraZeneca.

324

Nora: Real World Evidence in Renal Cell Carcinoma; A

National, Prospective, Non-Interventional Study in Patients

with Advanced/Metastatic Renal Cell Carcinoma Starting 1st

Line Nivolumab and Ipilimumab Combination Therapy or

Nivolumab Monotherapy After Prior Therapy

Harald Müeller-Huesmann 1; Jens Bedke 2; Viktor Grünwald 3; Hanjo Belz 4;

Martin Bögemann 5; Martin Herber 6; Eyck von der Heyde 7; Philipp Ivanyi 8;

Albrecht Kretzschmar 9; Martin Schostak 10; Wolfgang Schultze-

Seemann 11; Marc-Oliver Grimm 12

1Department of Internal Medicine, Hematology and Oncology

Brüderkrankenhaus St. Josef, Paderborn

2Department of Urology, Eberhard Karls University, Tübingen

3Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University

Hospital Essen, Essen

4Zeisigwaldkliniken, Chemnitz

5University Hospital Muenster, Muenster

6Bristol-Myers-Squibb GmbH & Co. KGaA, München

7Studienzentrum am Raschplatz, Hannover

8Department of Hematology, Hemostasis, Oncology and Stem Cell

Transplantation, Hannover Medical School, Hannover

9MVZ Mitte Onkologische Schwerpunktpraxis, Leipzig

10Department of Urology and Pediatric Urology, University Hospital Magdeburg,

Magdeburg

11Department of Urology, Medical Center - University of Freiburg, Faculty of

Medicine, University of Freiburg, Freiburg

12Department of Urology, Jena University Hospital, Jena

Purpose: e pivotal Ph3 trials CM 214 (NCT02231749) and CM 025

(NCT01668784) showed long term overall survival benet for patients

with advanced/metastatic RCC treated with nivolumab + ipilimumab

combination therapy compared to sunitinib and for nivolumab alone vs.

everolimus. Real world data is needed to further evaluate the eectiveness

and tolerability in routine clinical care, as well as the quality of life associ-

ated with the treatment in a broader patient population.

Materials: NORA (NCT02940639) is an ongoing, non-interventional

study (NIS) in Germany. Overall, 490 adult patients diagnosed with ad-

vanced/metastatic RCC, who start a new systemic 1st line therapy with

nivolumab + ipilimumab with intermediate/poor risk (cohort-2, n=260)

or nivolumab aer prior therapy (cohort-1, n=230) according to market-

ing authorization in Germany, will be enrolled. Patients are followed for

5 years from treatment initiation until death, withdrawal of consent, loss

to follow-up or end of study. e primary endpoint is overall survival.

Secondary endpoints include progression free survival, response rates, ad-

verse events (AE), AE management and patient reported outcomes with

EQ-5D and FKSI19.

Results: At the September 30th 2019 data cut, 36 months aer start of

enrollment, interim data of 233 patients of cohort-1 describe baseline

characteristics and outcome of patients with a minimum follow-up of 6

months. e data also shows demographic and disease characteristics,

ECOG performance status and patient reported outcomes for 1st line pa-

tients documented until data cut.

Conclusion: We provide the rst eectiveness data of the NORA obser-

vational study in patients treated with nivolumab monotherapy in routine

care in Germany. Furthermore, information about baseline characteristics

in 1st line patients and the management of immune related adverse events

in clinical practice is shown. Taken together, these data give valuable in-

sight in the current treatment landscape and outcome in patients with ad-

vanced/metastatic RCC.

326

Successful Targeting of the Warburg Eect in Prostate

Cancer by Novel 1,4-Naphthoquinone Sulphomethylene

Carbohydrate Conjugates

Tobias Busenbender 1; Sergey Dyshlovoy 1, 2; Moritz Kaune 1;

Jessica Hauschild 1; Dmitry N. Pelageev 3; Valentin A. Stonik 3;

Markus Gräfen 2; Carsten Bokemeyer 1; Gunhild von Amsberg 1, 2

1Zentrum für Onkologie, II. Medizinische Klinik und Poliklinik (Onkologie,

Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie,

Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

2Martini-Klinik Prostate Cancer Center, Universitätsklinikum Hamburg-

Eppendorf, Hamburg, Deutschland

3G.B. Elyakov Pacic Institute of Bioorganic Chemistry, Far Eastern Branch

Russian Academy of Science, Vladivostok, Russland

Purpose: e ability of prostate cancer (PCa) cells to consume large

amounts of glucose due to overexpression of GLUT11 (Warburg eect)

can be used to enhance selectivity of anticancer drugs by their conjugation

to carbohydrates. 1,4-naphtoquinones exhibit cytotoxic eects by exerting

oxidative stress on cancer cells.2 Here, we characterize a series of novel

semi-synthetic molecules containing a 1,4-naphthoquinone conjugated

with glucose via S-CH2 bond.

Methods: A cytotoxicity screen was performed for the 34 novel com-

pounds in 22Rv1 cells by MTT assay. e two most active compounds

were evaluated in human PCa cells, as well as non-malignant cells to

conrm selectivity. Apoptosis induction, mitochondrial damage, oxida-

tive stress and glucose uptake were assessed by Western Blot and FACS

analysis.

Results: Two promising derivatives with IC50s of low micromolar

concentrations and high selectivity for PCa cells were identied in the

screen. Glucose depletion in media resulted in increased cytotoxicity

of the compounds, while GLUT1-inhibitors antagonized these eects,

suggesting a GLUT1-mediated uptake of the derivatives. Up-regulation of

cleaved caspase-3, cleaved PARP and Bax indicate an apoptotic character

of drug-induced cell death. At the same time, pro-survival pathways

(Bcl-2, Survivin) were suppressed under treatment. e compounds

reduced mitochondrial membrane potential, increased ROS levels and

the antioxidant N-acetylcysteine rescued treated cells from cell death,

suggesting oxidative stress to contribute to the cytotoxic activity. Strong

synergistic eects were observed in combination with PARP inhibitors.

Conclusions: We identied two novel compounds exhibiting potent ac-

tivity and selectivity in human PCa cells due to GLUT1-mediated uptake.

e mode of action comprises caspase-dependent apoptosis, suppression

of pro-survival processes and induction of oxidative stress. Eects on AR-

and MAPK-signaling, cancer cell proteome and autophagy are currently

investigated.

References:

1. Pertega-Gomez et al. J. Pathol 2015

2. Wellington RSC 2015

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335

Survival Improvement in Metastatic Renal Cell Carcinoma

(MRCC) Patients Over Time: Do Elderly Patients Participate?

Hendrik Eggers 1; Viktor Grünwald 2; Linda Rudolph 1;

Maria-Louisa Tiemann 1; Christoph Reuter 1; Ganser Arnold 1;

Philipp Ivanyi 1

1Hannover Medical School, Department of Hematology, Hemostasis, Oncology

and Stem Cell Transplantation, Hannover Medical School, Hannover, Hannover,

Deutschland

2Essen University Hospital, Interdisciplinary Genitourinary Oncology at the

West-German Cancer Center, Clinic for Internal Medicine (Tumor research) and

Clinic for Urology, Essen, Deutschland

Purpose: e incidence of RCC is increasing and prognosis of mRCC

is still limited. However, new approaches have changed our therapeutic

landscape dramatically over the last two decades and overall survival (OS)

for mRCC is improving. Nonetheless, little is known about the outcome of

elderly mRCC patients. erefore, this monocentric retrospective analysis

addresses changes in overall survival between treatment periods and age

groups.

Methods: Patients with mRCC treated at Hannover Medical School from

01/2003 - 12/2018 were identied by retrospective chart review. Treat-

ment periods were dened from 01.01.2003 – 31.12.2009 (Period 1) and

01.01.2010 – 31.12.2018 (Period 2). Age groups were dened according

to WHO (age <61 years = not old, age 61-75 = older, age >76 = old). De-

scriptive statistics, Kaplan-Meier analysis and logistic regression were ad-

ministered.

Results: Overall, 314 patients showed a median OS of 40.1 months (95%-

CI: 32.8-47.4 month). Median OS is signicantly longer for patients

treated in period 2 vs. period 1 (59.1 vs. 35.1 months, p=0.003). Median

OS does not dier between not old vs. older and older vs. old. Subgroup

analysis of age groups within treatment periods showed no dierence, but

increase of median OS was more profound in age group old vs older com-

paring treatment periods (period 1 older 36.7, period 1 old 18.8, period 2

older 59.1, period 2 old 45.7 months).

Conclusions: While the increase in OS between treatment periods might

reect the advance of our therapeutic armamentarium, there is no dier-

ence in OS comparing age groups. Improvement of OS was comparable

between age groups, but with the largest increase in median OS across

treatment periods. Surprisingly, the old seem to prot particularly.

337

Prognostic Role of Docetaxel-Induced Reduction of Free

Testosterone Serum Levels in Metastatic Prostate Cancer

Patients

Paula Kappler 1; Michael Morgan 2; Philipp Ivanyi 1; Arnold Ganser 1;

Christoph Reuter 1

1Hämatologie, Hämostaseologie, Onkologie & Stammzelltransplanation,

Medizinische Hochschule Hannover, Hannover, Deutschland

2Experimentelle Hämatologie, Medizinische Hochschule Hannover, Hannover

Purpose: We have recently demonstrated that carboplatin plus weekly

docetaxel is eective in docetaxel-refractory prostate cancer (PC) and in-

terferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat.

2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monother-

apy on free and total testosterone (fT, TT) serum levels and the prognostic

role of fT and TT were analyzed in mPC patients.

Methods: 59 consecutive mPC patients were treated with at least two cy-

cles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until

disease progression, occurrence of intolerable adverse eects or comple-

tion of the planned cycle number. Ecacy measures were done following

PCWG2 recommendations. FT and TT were measured before and during

chemotherapy.

Results: At the current analysis, the median follow-up time was 20.8

months. Response of prostate-specic antigen (PSAR; ≥50% PSA reduc-

tion) was observed in 39/59 (66.1%) and 11/37 (29.7%) patients with

measurable disease exhibited a partial remission (PR). Median progres-

sion-free survival (PFS) for all patients was 7.8 months (CI 95% 3.8, 11.8)

and median overall survival (OS) was 25.1 months (CI 95% 17.6, 32.7).

e most common reversible grade 3/4 toxicity was leukopenia/neutrope-

nia (29.3/34.5%). Median fT and TT serum levels were reduced below the

detection limit during docetaxel treatment (fT: from 0.37 pg/mL to <0.01

pg/mL and TT: from 0.12 to <0.05 ng/mL, respectively). Multivariate Cox

regression analyses identied fT nadir values <0.01 pg/mL, PSAR>50%,

number of organs involved and previous prednisone treatment as inde-

pendent prognostic risk factors for PFS and fT reduction >90%, number

of organs involved and previous prednisone as independent prognostic

risk factors for OS. FT nadir values <0.01 pg/mL and PSAR >50% were

associated with longer PFS (p<0.05).

Conclusions: ese data demonstrate that fT is an important prognostic

factor for PFS and OS in mPC patients.

Disclosure Statement: e authors declare no potential conicts of interest.

391

Advanced Renal Cell Carcinoma: First Results from the

Prospective Research Platform Carat for Patients with MRCC

in Germany

Peter J Goebell 1; Lothar Müller 2; Carsten Grüllich 3; Dietmar Reichert 4;

Martin Bögemann 5; Steen Dörfel 6; Eyck von der Heyde 7;

Adrian Binninger 8; Martina Jänicke 8; Norbert Marschner 9;

Michael Staehler 10; Viktor Grünwald 11

1Waldkrankenhaus St. Marien Urologische Universitätsklinik, Erlangen,

Deutschland

2Onkologie UnterEms Leer-Emden-Papenburg Dr. L. Müller, C. Janßen, Leer,

Deutschland

3Universitätsklinikum Carl Gustav Carus, Dresden, Deutschland

4Gemeinschaftspraxis für Hämatologie und Onkologie, Westerstede,

Deutschland

5Universitätsklinikum Münster (AöR), Münster, Deutschland

6Onkozentrum Dresden/Freiberg, Dresden, Deutschland

7Onkologische Schwerpunktpraxis, Hannover, Deutschland

8iOMEDICO, Freiburg, Deutschland

9Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland

10Klinikum der Universität München Campus Großhadern, München,

Deutschland

11Universitätsklinikum Essen, Essen, Deutschland

Purpose: e Tumor Registry Renal Cell Carcinoma (TNK) analyzed

treatment and outcome of patients (pts) treated in Germany from 2007-

17. CARAT is the successor registry, which continues to assess longitudi-

nal real world clinical outcome, incl. patient-reported outcomes (PROs)

and decentralized biobanking. Today, we introduce CARAT and report

on current changes of the treatment landscape in mRCC in Germany.

Methods: Since Dec 2017 150 pts have been enrolled in CARAT, expand-

ing the previous TNK (2007-17, 1500 pts). CARAT is an observational,

prospective, open, multicenter clinical research platform aiming to enroll

1000 pts by 150 sites. Pts with mRCC who start systemic 1stline treatment

are eligible. Treatment characteristics, clinical outcome and physician-re-

ported factors on treatment decision making are collected. Changes of the

treatment landscape are shown descriptively.

Results: By August 2019 >1700 pts with mRCC have been recruited. Me-

dian age is 68 years. 60% had intermediate risk (MSKCC) at start of 1st-

line. Median OS for pts with start of 1st-line 2007-17 is 19 months (>60%

events). If selected by trial eligibility criteria, the median OS is 27 months.

Pts who started treatment in 2018 mostly received pazopanib or sunitinib

(38%/34%). Since the approval (May 2018) 18% are treated with cabozan-

tinib. Preferred 2nd-line treatment changed from sorafenib/temsirolimus

(35%/21%, 2007-09), everolimus (33% 2010-12), everolimus/axitinib/

sunitinib (29%/19%/18%, 2013-15) to nivolumab (>60% since 2016). e

impact of new treatment options on OS will be analyzed.

Conclusions Pts in routine care in Germany are older and have inferior

prognosis than trial-eligible pts. CARAT complements results of RCTs

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with prospective data on clinical and PROs for pts with mRCC in routine

care. CARAT will show changes in the choice of treatment due to new

approvals, applied sequences and investigate the eectiveness in a “real

world” setting.

Disclosure Statement: None of the authors declare conicts of interests regarding

the topic of this abstract.

414

Early Mortality of Prostatectomy vs. Radiotherapy as a

Primary Treatment for Prostate Cancer: a Population-Based

Study from The United States and East Germany

Daniel Medenwald; Dirk Vordermark; Christian Dietzel

Universität Halle, Halle (Saale), Deutschland

Purpose: To assess the extent of early mortality and its temporal course

aer prostatectomy and radiotherapy in the general population.

Methods: Data from SEER-database and East German epidemiologic can-

cer registries were used for the years 2005-2013. Metastasized cases were

excluded.

Analysing overall mortality, year-specic Cox regression models were

used aer adjusting for age (including age squared), risk stage and grad-

ing. To estimate temporal hazards we computed year-specic conditional

hazards for surgery and radiotherapy aer propensity-score matching and

applied piecewise proportional hazard models.

Results: In German and US-American populations we observed higher

initial three-month mortality odds for prostatectomy (USA: 9.4, 95% CI:

7.8–11.2; Germany: 9.1, 95% CI: 5.1-16.2) approaching the null eect val-

ue not before 24 months (estimated annual mean 36 months in US data)

aer diagnosis.

During the observational period we observed a constant hazard ratio for

the 24-month mortality in the US-population (2005: 1.7, 95% CI: 1.5–1.9;

2013: 1.9, 95% CI: 1.6–2.2) comparing surgery and radiotherapy. e

same was true in the German cohort (2005: 1.4, 95% CI: 0.9–2.1; 2013:

3.3, 95% CI: 2.2–5.1). Considering low-risk cases, the adverse surgery ef-

fect appeared stronger.

Conclusions: ere is strong evidence from two independent populations

of a considerably higher early to midterm mortality aer prostatectomy

compared to radiotherapy extending the time of early mortality consid-

ered by previous studies up to 36 months (at least 24 months).

Disclosure Statement: All authors declare that there is no conict of interest.

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463

TKI Induction Followed by a Randomized Comparison

between Nivolumab or TKI Continuation in Renal Cell

Carcinoma (NiVOSWiTCH)

Viktor Grünwald 1; Carsten Grüllich 2; Philipp Ivanyi 3; Manfred Wirth 4;

Peter Staib 5; Martin Schostak 6; Philip Dargatz 7; Lothar Müller 8;

Michael Metz 9; Lothar Bergmann 10; Thomas Steiner 11; Manfred Welslau 12;

Anja Lorch 13; Philipp Schütt 14; Mohamed-Reza Rayan 15; Eva Hellmis 16;

Axel Hinke 17; Martin Mänz 18; Johannes Meiler 19; Thomas Kretz 20;

Wolfgang Loidl 21; Anne Flörcken 22

1Universitätsklinikum Essen , Klinik und Poliklinik für Urologie, Essen,

Deutschland

2Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

3Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,

Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,

Deutschland

4Universitätsklinikum „Carl Gustav Carus“ der Technischen Universität Dresden,

Klinik und Poliklinik für Urologie, Dresden, Deutschland

5St.-Antonius-Hospital, Hämatologie/Onkologie, Eschweiler, Deutschland

6Universitätsklinikum Magdeburg, Klinik für Urologie, Magdeburg, Deutschland

7Johannes Wesling Klinikum Minden, Klinik für Hämatologie/Onkologie,

Minden, Deutschland

8Onkologie UnterEms Leer, Leer (Ostfriesland), Deutschland

9ConMed GmbH, Göttingen, Deutschland

10Universitätsklinikum Frankfurt, Medizinische Klinik II, Frankfurt am Main,

Deutschland

11Helios Klinikum Erfurt, Klinik für Urologie, Erfurt, Deutschland

12Onkologie Aschaenburg, Hämato-Onkologische Schwerpunktpraxis am

Klinikum Aschaenburg, Aschaenburg, Deutschland

13UniversitätSpital Zürich, Klinik für Medizinische Onkologie und Hämatologie,

Zürich, Schweiz

14Onkologische Schwerpunktpraxis, Gütersloh, Deutschland

15Krankenhaus Nordwest, Klinik für Onkologie und Hämatologie, Frankfurt am

Main, Deutschland

16Urologicum Duisburg, Duisburg, Deutschland

17CCRC Cancer Clinical Research Consulting, Düsseldorf, Deutschland

18AIO-Studien-gGmbH, Berlin, Deutschland

19Klinik Dr. Hancken GmbH, Stade, Deutschland

20Urologie Heinsberg, Heinsberg, Deutschland

21Ordensklinikum Linz Barmherzige Schwestern, Linz, Österreich

22Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt

Hämatologie, Onkologie und Tumorimmunologie, Berlin, Deutschland

Background: Treatment with tyrosine kinase inhibitors (TKI) or

Nivolumab (NIVO) are standard treatment options in metastatic renal cell

carcinoma (mRCC). We tested whether TKI with early switch to NIVO

improved outcome in mRCC.

Patients and methods: Key inclusion criteria: measurable advanced or

metastatic ccRCC, ECOG PS: 0-2, adequate organ function. Patients with

PR or SD to sunitinib or pazopanib aer 10-12 weeks of treatment were

1:1 randomized to continue TKI treatment or switch to NIVO 240 or 480

mg IV q2-4wks. Imaging was performed q12wks. 49 of 244 planned pa-

tients were randomized between December 2016 and August 2018 and

poor accrual led to premature closure of the trial. Ecacy and safety pa-

rameters were analyzed descriptively.

Results: 25 and 24 pts. received NIVO or TKI, respectively. Median age

was 65 years (range: 35-79), 40 pts. (82%) were male and 2 pts. (4%) had an

ECOG PS of 2. MSKCC risk categories were: favorable (31%), intermedi-

ate (65%), and poor (4%). Best objective response rate (ORR) from start of

1st line therapy was not signicantly dierent between groups (64 vs. 70%,

P=0.76). However, when measured from time of randomization ORR for

NIVO vs. TKI was 16 vs. 48% (P=0.029). All grades adverse events (AE)

occurred in 96% (NIVO) and 100% (TKI) and grade 3-5 were 44% vs.

67%, respectively. Serious AE (SAE) were 10 (40) and 9 (38), respectively.

Conclusions: Our results indicate that TKI-sensitive pts. have less ben-

et from early switch to NIVO treatment than from TKI continuation.

e major limitation of our trial is the premature closure and the limited

sample size.

Disclosure Statement: e authors declare no conict of interest.

Sponsor & funding source: AIO-Studien-gGmbH, nancial support: BMS

Clinical trial registry: Eudra-CT: 2016-002170-13. NCT02959554

488

Erdatinib Compared with Vinunine or Docetaxel or

Pembrolizumab in Patients (PTS) with Metastatic or Surgically

Unresectable (M/UR) Urothelial Carcinoma (UC) and Selected

FGFR Gene Alterations (FGFRALT): Phase 3 THOR Study

Florian Imkamp 1; Yohann Loriot 2; Andrea Necchi 3; Se Hoon Park 4;

Robert Huddart 5; Earle Burgess 6; Min Fu 7; Ademi Santiago-Walker 7;

Sutapa Mukhopadhyay 7; Vahid Naini 7; Kris Deprince 8; Manish Monga 7;

Arlene Siefker-Radtke 9

1Department of Urology, Hannover University Medical Center, Hannover,

Germany

2Institut Gustave Roussy, Villejuif, France

3Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

4Samsung Medical Center, Seoul, Korea

5Institute of Cancer Research, Sutton, London, UK

6Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North

Carolina, USA

7Janssen Research & Development, USA

8Janssen Research & Development, Beerse, Belgium

9University of Texas, MD Anderson Cancer Center, Houston, Texas, USA

Purpose: Pts with M/UR UC have poor prognoses. Programmed death

(ligand)-1 (PD-[L]1) inhibitors have improved outcomes in some pts,

but responses vary based on genotypic subtype. FGFRalt are present in

20% of pts with UC and may reect an immunologically cold tumor that

does not respond well to immunotherapy.1 In early phase 2 study, erda-

tinib (ERDA, 8 mg/d continuous), a pan-FGFR (1-4) inhibitor demon-

strated tolerability and favorable objective response rate (ORR, 42%)

in pts with M/UR UC and FGFRalt; uptitration to 9 mg/d was feasible.

Activity of single-agent ERDA will be compared with chemo or pem-

brolizumab in pts with M/UR UC in this randomized phase 3 study.

Methods: Adult pts (ECOG status ≤ 2, adequate bone marrow, liver, and

renal function; no uncontrolled cardiovascular disease, known HIV, hepa-

titis B or C, or baseline phosphate persistently above upper limit of normal

allowed) with stage 4 M/UR UC and specic pathogenic FGFRalt (FGFR3

mutations or FGFR2/3 fusions), who have received 1 or 2 lines of prior

systemic therapy are eligible. Pts will be screened for FGFRalt and ran-

domized in 2 cohorts (1:1). Cohort 1 (n ~280): pts with prior chemo and

PD-L1 inhibitor (prior PD-[L]1 inhibitor -as monotherapy or combo; no

more than 2 lines of prior allowed for cisplatin-ineligible pts) in combi-

nation or in maintenance setting will receive 8 mg/d continuous ERDA

vs chemo (1:1) with docetaxel or vinunine. Cohort 2 (n ~350): pts with

prior chemo but no prior PD-(L)1 inhibitor will receive 8 mg/d ERDA

vs pembrolizumab (1:1). Uptitration of ERDA to 9 mg/d is recommend-

ed in pts with serum phosphate ≤ 9 mg/dL. Primary end point: overall

survival. Secondary end points: progression-free survival, ORR, duration

of response, pt-reported outcomes, safety, and pharmacokinetics. PD-L1

expression level per immunohistochemistry and UC subtype per RNA

sequencing or other methods as exploratory end points. Pts are being en-

rolled at sites in 25 countries. For additional information on specic sites/

countries refer clinicaltrials.gov (NCT03390504).

Reference:

1. Sieer-Radtke ASCO GU 2018

495

Activity of Two Routine Cabazitaxel Treatment Sequences

in Patients with Metastatic Castration- Resistant Prostate

Cancer (mCRPC) – Interim Analysis of The Non-Interventional

Scope Study

Carsten Bokemeyer 1; Burkhard Otremba 2; Richard Cathomas 3;

Franz Stoiber 4; Jürgen Gschwend 5

1Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

2Onkologische Praxis Oldenburg/ Delmenhorst, Oldenburg, Deutschland

3Kantonsspital Graubünden, Chur, Schweiz

4Salzkammergut Krankenhaus Vöcklabruck, Abt.für Urologie, Vöcklabruck ,

Österreich

5Klinikum rechts der Isar der Technischen Universität München, München,

Deutschland

Purpose: Cabazitaxel (CAB) and new hormonal therapies (HT: abi-

raterone or enzalutamide) have demonstrated a survival benet in the

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post-docetaxel setting. Optimal sequencing of these agents is unknown.

SCOPE is the rst multinational, non-interventional study evaluating

prospectively the activity of CAB according to dierent sequences.

Methods: SCOPE is aimed at recruiting 900 patients (pts.) starting treat-

ment with CAB in daily practice. Medical history, previous life-extending

therapies received and outcome during CAB therapy (PSA response, clin-

ical benet, pain relief, tumor response as per RECIST) are collected. Pts

are followed for up to 24 months aer start of CAB therapy. Treatment

outcomes (PSA, clinical including pain or radiological) are collected. For

the current interim analysis (cut-o FEB 04, 2019) preliminary treatment

outcomes of 2 sequences of therapies (DOC-CAB-HT and DOC-HT-

CAB) are provided. It is funded by Sano-Aventis Germany.

Results: Of 734 enrolled pts., 273 pts. currently completed CAB therapy

and are included in this interim analysis. 150 pts. (55%; med. age 70

yrs) received DOC-CAB-HT and 123 received DOC-HT-CAB (45%,

med. age 73 yrs). Of these 273 pts, 146 (53.5%) responded to CAB (DOC-

CAB-HT, n=87; DOC-HT-CAB, n=59), 76 (27.8%) had no response - out-

come was missing for 51 (18.7%). Responses to CAB (n=146) documented

were mainly a PSA decrease (≥30% or ≥50% in 92 or 63 pts, respectively)

, pain relief (n=18), clinical (n=36) and RECIST responses (n=13; PR n=6

; SD n=7). Med. PFS with CAB was 4.9 mo (95% CI 4.0-5.5) with DOC-

CAB-HT and 4.6 mo (95% CI 3.9-5.4) with DOC-HT-CAB (p=0.24). OS

data are not yet mature. TEAE were observed in 141 pts. (51.7%). Main

AE of CAB ≥ 5% were nausea (7.3%), fatigue (6.3%), anemia (5 %) and

diarrhea (4.7%).

Conclusions: Preliminary results of SCOPE prospective registry suggest

that under routine conditions, CAB is active (even aer new HT) and

shows manageable tolerability.

Reference:

1. Oncol Res Treat 20149;42(suppl 4):51. Published and presented Oktober 2019

by same authors

530

Anticancer Activity and Mechanism of Action of Derivatives

of The Marine Alkaloid Ascididemine in Drug-Resistant

Prostate Cancer

Moritz Kaune 1; Sergey A. Dyshlovoy 1, 2, 3, 4; Jessica Hauschild 1;

Tina Rohlng 1; Dmitry N. Pelageev 3; Valentin Stonik 3; Markus Graefen 4;

Carsten Bokemeyer 1; Gunhild von Amsberg 5, 6

1Department of Oncology, Hematology and Bone Marrow Transplantation with

Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center

Hamburg-Eppendorf, Hamburg, Deutschland

2Department of Organic Chemistry and Laboratory of Biologically Active

Compounds , School of Natural Sciences, Far Eastern Federal University ,

Vladivostok, Russland

3G.B. Elyakov Pacic Institute of Bioorganic Chemistry, Vladivostok, Russland

4Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf,

Hamburg, Deutschland

5Department of Oncology, Hematology and Bone Marrow Transplantation with

Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center

Hamburg-Eppendorf, Hamburg, Deutschland

6Martini-Klinik Prostate Cancer Center, University Medical Center Hamburg-

Eppendorf, Hamburg, Deutschland

Purpose: Marine organisms have served as a source for new potent anti-

cancer drugs. e marine natural compound Ascididemine, a pentacyclic

aromatic alkaloid, is known to exhibit antineoplastic activity.

Methods: Chemically optimized synthetic Ascididemine derivatives were

generated and screened for selective cytotoxicity against human prostate

cancer (PCa) cells. Most promising compounds were chosen for further

investigations in vitro. Eects on cell compartments, intracellular signal-

ing, proteome and kinome were investigated. Combinational treatment

with established and preclinical drugs were performed. Androgen-inde-

pendent, docetaxel-resistant PC3 cells and AR-V7 positive, BRCA2- mu-

tated 22Rv1 cells were investigated.

Results: Two out of 24 derivatives were identied to selectively and po-

tently inhibit drug-resistant PCa cells, while non-malignant cells were less

aected. e compounds induced a mitochondrial membrane- permea-

bilization followed by increase of reactive oxygen species levels and Ca2+

release by the endoplasmatic reticulum. Decreasing levels of intracellular

androgen receptor and its splice variant ARV7 were found. Kinome and

proteome analysis revealed a general upregulated kinomic activity, spe-

cically for the PI3K-Akt-pathway and PIM1 kinase. Coherently, combi-

nations with specic Akt inhibitors as well as PARP inhibitor Olaparib in

BRCA2-decient PCa cells revealed strong synergism. Moreover a syner-

gism in drug-resistant PCa cells was found for abiraterone, enzalutamide

and docetaxel, indicating a reconstitution of sensitivity to these anticancer

drugs.

Conclusions: We identied two potent marine-derived anticancer sub-

stances with high potential to overcome resistance mechanisms alone

and in combination with established drugs in PCa, thus lling a medical

demand. e mechanism of action includes the induction of mitochon-

drial damage leading to Ros generation and activation of endoplasmatic

reticulum stress with consequent caspase-dependent apoptosis. In vivo

examinations are ongoing.

546

Ecacy of Anti-PD(L)1 Treatment in Patients with Metastatic

Urothelial Cancer Based on mRNA- and Protein- Based PD-L1

Determination: Results from the Multicentric, Retrospective

Fosmic Trial

Jonas Jarczyk 1, 2; Ralph M. Wirtz 2, 3; Florian Roghmann 2, 4; Hendrik Jütte 2, 5;

Maximilian C. Kriegmair 1, 2; Thomas S. Worst 1, 2; Danijel Sikic 2, 6;

Sven Wach 2, 6; Helge Taubert 2, 6; Bernd Wullich 2, 6; Veronika Weyerer 2, 7;

Robert Stoehr 2, 7; Friedemann Zengerling 2, 8; Christian Bolenz 2, 8;

Johannes Breyer 2, 9; Maximilian Burger 2, 9; Stefan Porubsky 2, 10;

Arndt Hartmann 2, 7; Philipp Erben 1, 2; Markus Eckstein 2, 7

1Department of Urology, University Hospital Mannheim, University of

Heidelberg

2On behalf of the BRIDGE-Consortium e.V.

3STRATIFYER Molecular Pathology GmbH, Cologne

4Department of Urology, Marien-Hospital Herne, University Hospital Bochum,

University of Bochum

5Department of Pathology, University Hospital Bochum, University of Bochum

6Department of Urology and Pediatric Urology, University Hospital Erlangen,

University of Erlangen-Nuernberg

7Institute of Pathology, University Hospital Erlangen, University of Erlangen-

Nuernberg

8Department of Urology, University Hospital Ulm, University of Ulm

9Department of Urology, Caritas Hospital St. Josef, University of Regensburg

10Department of Pathology, University Hospital Mannheim, University of

Heidelberg

Purpose: Immunotherapy (IO) against PD1 or PD-L1 has been approved

for treatment of metastasized urothelial bladder cancer (mUC). Here we

evaluated ecacy in a retrospective Real-World-Phase IV trial based on

molecular subtypes and PD-L1 status.

Methods: Cancer specic survival (CSS) from start of IO treatment to

death was analyzed in a multicenter cohort of 65 patients having received

IO for mUC in 1st and 2nd line setting. Intrinsic molecular subtypes were

assessed by CK5, CK20, GATA3, FOXA1 and CD44 immunohistochem-

istry and RT-qPCR of CK5 and CK20. PD-L1 status was determined us-

ing the 28-8 Dako-assay. Stromal tumor inltrating lymphocytes were

assessed on HE slides. Survival analyses were performed by applying

clinically relevant cut-os and using Kaplan-Meier analysis and logistic

regression for CSS.

Results: Altogether, 43% of tumors presented with basal dierentiation,

57% were luminal. As expected, basal tumors exhibited signicantly high-

er levels of PD-1 and PD-L1 gene expression, higher amounts of sTILs and

PD-L1+ immune and tumor cells. Hierarchical clustering of all immuno-

logical biomarkers revealed three cluster: “Inamed high” (n=13, 20%),

“Inamed low” (n=22, 33.8%), and “Uninamed” (n=30, 46.2%). ere

were no signicant CSS dierences for any of these groups. However, pa-

tients with good performance status (ECOG0) and low PD-L1 expression

showed signicantly better CSS compared to those with ECOG0 / PD-L1

high and ECOG1 or ECOG2, respectively.

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Conclusions: Immunological determinants of mUC show comparable

distributions and correlations with subtypes of localized curatively treated

MIBC patients. Interestingly, data indicate improved CSS aer PD-1/PD-

L1 treatment in patients with good performance and low PD-L1 expres-

sion, which warrants validation in larger cohorts.

Disclosure Statement: Stratifyer carried out gene expression analysis, RW is

owner and employee of Stratifyer. Janssen Pharmaceutical gave research support

for this work. is abstract was submitted at Esmo 2019.

610

Prognostic Role of FGFR Mutations and FGFR mRNA

Expression in Metastatic Urothelial Cancer Treated with

Anti-PD(L1) Inhibitors in First an Second Line Setting

Florian Roghmann 1, 2; Ralph Wirtz 2, 3; Ademi Santiago-Walker 4;

Jonas Jarczyk 2, 5; Maximilian Kriegmair 2, 5; Thomas Worst 2, 5; Danijel

Sikic 2, 6; Sven Wach 2, 6; Helge Taubert 2, 6; Veronika Weyerer 2, 7; Robert

Stöhr 2, 7; Friedemann Zengerling 2, 8; Christian Bolenz 2, 8; Johannes Breyer 2, 9;

Maximilian Burger 2, 9; Stefan Porubsky 2, 10; Arndt Hartmann 2, 7;

Philipp Erben 2, 5; Markus Eckstein 2, 7; Hendrik Jütte 2, 11

1Department of Urology, Ruhr-University Bochum, Marien Hospital , Herne,

Deutschland

2on behalf of the BRIDGE-consortium e.V

3STRATIFYER Molecular Pathology GmbH, Cologne

4Janssen-Cilag GmbH, Deutschland

5Department of Urology, University Hospital Mannheim, Ruprecht-Karls-

University Heidelberg, Mannheim

6Department of Urology and Pediatric Urology, University Hospital Erlangen,

Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen

7Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander

Universität Erlangen-Nürnberg, Erlangen

8Department of Urology, University Hospital Ulm, University of Ulm, Ulm

9Department of Urology, Caritas Hospital St. Josef, University of Regensburg,

Regensburg

10Department of Pathology, University Hospital Mannheim, Ruprecht-Karls-

University Heidelberg, Mannheim

11Department of Pathology, University Hospital Bochum, University of Bochum,

Bochum

Purpose: In the era of individualized oncological therapy in bladder can-

cer, FGFR3 mutations, FGFR2 and FGFR3 gene fusions as well as FGFR

mRNA expression as potential oncological targets and their association to

anti-PD-1 and anti-PD-L1 (IO) treatment outcomes in patients with met-

astatic urothelial cancer of the bladder (mUCB) was studied in a German

patient cohort.

Methods: Within a cohort of 72 patients with mUCB from 5 academic

centers in Germany (2016-2018) FGFR3 mutations, FGFR2 and FGFR3

gene fusions as well as FGFR expression in formalin-xed, paran em-

bedded tumour samples and its association to survival was examined

using SNaPshot PCR, RT-qPCR as well as Next Generation Sequencing.

Statistical analyses comprised Kaplan-Meier survival analyses, Spearman

rank correlations, non- parametric testing.

Results: In 17% of all patients, FGFR3 mutations or gene fusions could

be detected. Patients with FGFR3 alterations did not have better outcome

aer IO treatment (p=0.201). All alterations of FGFR3 resulted in overex-

pression of FGFR3 mRNA. Combination of FGFR mutation analysis and

FGFR mRNA assessment improved IO outcome prediction. Overexpres-

sion of FGFR3 mRNA was negatively associated with PDL1 expression

(mRNA and protein level). High FGFR2 mRNA expression in primary tu-

mors predicted better disease specic survival of mUCB patients receiving

IO therapy, whereas high FGFR3 mRNA expression was associated with

tumor specic death in patients exhibiting of low FGFR2 mRNA expres-

sions (p<0.05). is high risk group of mUCB patients exhibiting high

mRNA levels FGFR3 comprises 40% of the total cohort.

Conclusions: e assessment of FGFR mRNA by standardized RT-qPCR

identied a high risk mUCB patient cohort, which has inferior disease

specic survival despite IO treatment and overexpresses FGFR3 mRNA.

e assessment of FGFR mRNA levels by using this standardized, locally

applicable FGFR testing could identify an FGFR inhibitor target popula-

tion with poor response to IO treatment which is twice the size as current-

ly detected by FGFR genomic alterations alone.

619

Objectively Assessed Physical Activity and Sedentary

Behavior in Patients with Advanced Renal Cell Carcinoma

Christiane Hering-Schubert 1; Philipp Zimmer 2; Kathrin Schlüter 3;

Sybill Heßler 3; Valérie Perrot 4; Heiko Wunderlich 1

1St. Georg Klinikum Eisenach, Eisenach, Deutschland

2Deutsche Sporthochschule Köln, Köln, Deutschland

3IPSEN Pharma GmbH, Ettlingen, Deutschland

4IPSEN, Boulogne-Billancourt, Frankreich

Purpose: Increased levels of physical activity are associated with decreased

cancer risk and mortality in many cancer types. Moreover, physical ac-

tivity is known to reduce several side eects of cancer and its treatment

thereby improving patients’ quality of life (QoL). So far, most studies have

focused on frequently observed types of cancer, such as breast-, prostate-,

lung- and colorectal carcinoma. Recent data from epidemiological studies

also reported such relationships for renal cell carcinoma (RCC). Obser-

vational studies have included heterogenous populations in view of stage

of disease and treatment. Further, collected data on physical activity have

been based on self-reported assessments, a major limitation of these trials.

Methods: Against this backdrop we have initialized the multicenter ob-

servational CABOCARE trial in Germany and Austria. Patients with ad-

vanced RCC (n = 105) are recruited aer treatment decision for cabozan-

tinib has been made. Cabozantinib is an inhibitor of receptor tyrosine

kinases c-MET, VEGFR and AXL, which has proven to prolong progres-

sion free survival (PFS) compared to standard care with sunitinib. Patient

characteristics, state of disease, occurrence of adverse events (AE), quality

of life (FACT NFKSI-19), self-reported physical activity (newly developed

visual analogue scales) as well as objective physical activity, sedentary

behavior and sleep data (Actigraph® GT9X Link device) are recorded at

baseline, and each three months thereaer.

Results: Until data cut-o, baseline physical activity data were available

for three patients showing that the patients’ subjective and objective phys-

ical activity results were similar. e patients recorded predominately

light physical activity, and the mean time of moderate to vigorous physical

activity was below the recommended value of 150 minutes per week.

Conclusions: CABOCARE (NCT03647878) will be the rst observational

trial collecting objective physical activity and sleep data and their associ-

ations with PFS, AE and QoL in patients with advanced RCC in a longi-

tudinal fashion.

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2018

634

Dierent Diagnostic Methods for Identication of FGFR

Alteration in Advanced Urothelial Carcinomas: Prociency

ResultsBased on Multiple RNA Extraction Kits and Mutation

Detection Methods

Veronika Weyerer 1; Robert Stöhr 2; Hendrik Jütte 3; Ralph Wirtz 4;

Markus Eckstein 5; Florian Roghmann 6; Johannes Breyer 7; Stefan

Porubsky 8; Danijel Sikic 9; Christian Bolenz 10; Maximilian Kriegmair 11;

Arndt Hartmann 5; Philipp Erben 11

1Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander

University Erlangen-Nürnberg, Erlangen, Deutschland

2Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander

University Erlangen-Nürnberg

3Institute of Pathology, Ruhr University Bochum, Bochum, Deutschland

4STRATIFYER Molecular Pathology GmbH, Cologne, Deutschland

1Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander

University Erlangen-Nürnberg, Erlangen, Deutschland

6Department of Urology, Ruhr University Bochum, Bochum, Deutschland

7Department of Urology, University of Regensburg, Regensburg, Deutschland

8Institute of Pathology, Medical Faculty Mannheim, University of Heidelberg,

Mannheim, Deutschland

9Department of Urology and Pediatric Urology, , University Hospital Erlangen,

Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Deutschland

10Department of Urology, University of Ulm, Ulm, Deutschland

11Department of Urology, Medical Faculty Mannheim, University of Heidelberg,

Mannheim, Deutschland

Purpose: Pan FGFR inhibitors such as Erdatinib are approved in patients

with advanced urothelial carcinoma (aUC) harboring FGFR alterations.

Based on the necessity of sensitive and reproducible identication of these

alterations in diagnostic routines this study aimed to compare dierent

RNA isolation techniques and the QIAGEN therascreen® FGFR RGQ RT-

PCR Kit with the SNaPshot mutational analysis.

Methods: Nucleic acids were extracted from 47 UC patients using the

QIAGEN RNeasy DSP FFPE Kit, STRATIFYER Xtract or Maxwell RNA

(Promega) isolation kit. Mutations of the FGFR3 gene were detected using

the SNaPshot method as well as via the QIAGEN therascreen® FGFR RGQ

RT-PCR Kit. Intrinsic molecular subtypes were assessed using immuno-

histochemistry (IHC) of GATA3, FOXA1, CK20, CK5 and CD44 as well

as RT-qPCR for gene expression of CK20 and CK5.

Results: All three dierent RNA isolation kits showed comparable amount

of extracted RNA (Median 290, 177 and 226 ng/ul). Six hotspot FGFR3

mutations were identied with 100% concordance. e main dierence

were the necessary working hours: per 10 samples, 4 vs. 4.5 vs 8 hours

were needed for Stratifyer, Maxwell or QIAGEN RNA isolation. In addi-

tion, of 47 analyzed samples 100% concordance between QIAGEN ther-

ascreen® FGFR RGQ RT-PCR Kit and SNapShot analysis were achieved

with 18 mutations identied (14 S249C, 2 R248C and 2 Y375). Immuno-

histochemical basal marker prole (CD44 and CK5) as well as high CK5

expression was observed in 28 (6/28 FGFR3-altered). Luminal marker

prole (IHC markers: GATA3, FOXA1 and CK20 as well as expression

of CK20) was detected in 37 samples (5/37 with FGFR3 alteration, n.s.).

Conclusions: Dierent RNA extraction methods presented with compa-

rable amount of nucleic acids with variant working hours. Moreover, a

100% concordance between the well established SNaPshot analysis com-

pared to the QIAGEN therascreen® FGFR RGQ RT-PCR Kit for FGFR3

mutations was observed. So far, the frequency of FGFR3 mutations in aUC

was not related to the type of UC as dened by marker proles.

676

Central, Prospective Detection of Homologous Recombination

Repair (HRR) Gene Alteration in Tumor Tissue From> 4000

Men with Metastatic Castration-Resistant Prostate Cancer

(mCRPC) Screened for The Profound Study

A Stenzl 1; M Hussain 2; K Fizazi 3; F Saad 4; N Shore 5; S Sandhu 6; N Mehra 7;

MKolinsky 8; G Roubaud 9; M özgüroğlu 10; N Matsubara 11; C Gedye 12;

Yd Choi 13; C Padua 14; C Goessl 15; A Kohlmann 16; C Corcoran 16;

CaAdelman 16; AAllen 15; J Burgents 17; J de Bono 18

1Department of Urology, Eberhard-Karls-University, Tübingen, Deutschland

2Robert H Lurie Comprehensive Cancer Center, Northwestern University

Feinberg School of Medicine, Chicago, United States

3Institut Gustave Roussy, University of Paris Sud, Villejuif, Frankreich

4Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, Kanada

5Carolina Urologic Research Center, Myrtle Beach, United States

6Peter MacCallum Cancer Centre, Melbourne, Australien

7Radboud University Medical Center, Nijmegen, Niederlande

8University of Alberta Cross Cancer Institute, Edmonton, Kanada

9Institut Bergonié, Bordeaux, Frankreich

10Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul,

Turkey

11National Cancer Center Hospital East, Chiba, Japan

12Calvary Mater Newcastle, Waratah, Australien

13Yonsei University College of Medicine, Seoul, Südkorea

14Cetus Medicina Oncológica, Betim, Brasilien

15AstraZeneca, Gaithersburg, United States

16AstraZeneca, Cambridge, United Kingdom

17Merck & Co, Inc, Kenilworth, United States

18The Institute of Cancer Research and Royal Marsden, London, United Kingdom

Purpose: A proportion of patients (pts) with mCRPC have tumor cells

harboring HRR gene alterations that may confer sensitivity to PARP inhi-

bition. e PROfound study (NCT02987543) is a phase III, randomized,

multicenter trial evaluating the ecacy and safety of the PARP inhibitor

olaparib versus physician’s choice of enzalutamide or abiraterone acetate

in pre-treated mCRPC pts with a qualifying alteration in 15 predened

genes with a direct or indirect role in HRR. Here, we report the prevalence

of single and co-occurring HRR alterations in pts screened for PROfound.

Methods: An investigational next-generation sequencing assay developed

in partnership with Foundation Medicine Inc. (FMI) was used to

prospectively select patients harboring HRR gene alterations in their

tumor tissue reporting deleterious or suspected deleterious qualifying

alterations in 15 HRR genes. Samples were clinically heterogenous

regarding location and timing. Pts with a qualifying alteration who met

the eligibility requirements were randomized to the trial. e study

comprised two cohorts; Cohort A: pts with alterations in BRCA1, BRCA2

or ATM (assigned regardless of any co-occurring mutation in other

genes); Cohort B: 12 other HRR genes.

Results: Of 4425 screened pts, 4047 had samples tested at FMI, of whom

2792 (69%) yielded a biomarker status result. A qualifying HRR alteration

was detected in 778 (27.9%) pts. Among the Cohort A genes, alterations

in BRCA2 were the most common (9.7%) followed by ATM (6.3%) and

BRCA1 (1.3%). CDK12 alterations (7.1%) were the most common among

the other HRR genes. A co-occurring qualifying HRR alteration in more

than 1 gene was detected in 59 (7.6%) patients, most commonly BRCA2

(n=30), CDK12 (n=24) or ATM (n=13).

Conclusions: is is the largest study to date with central prospective

HRR gene alteration tissue testing in prostate cancer. HRR alterations

were most common in BRCA2; followed by CDK12 and ATM. Further

analyses are warranted to help understand whether there is a correlation

between clinical/demographic characteristics and HRR alterations.

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2018

720

Role of Free Testosterone Serum Levels During Salvage

Chemotherapy with Carboplatin Plus Weekly Docetaxel in

Patients with Docetaxel-Refractory, Metastatic Castration-

Resistant Prostate Cancer (mCRPC)

Stefan Brunotte 1; Paula Kappler 1; Philipp Ivanyi 1; Michael Morgan 2;

Christoph von Klot 3; Christoph Reuter 1

1Hämatologie, Hämostaseologie, Onkologie, Stammzelltransplantation,

Medizinische Hochschule Hannover, Hannover, Deutschland

2Experimentelle Hämatologie, Medizinische Hochschule Hannover, Hannover,

Deutschland

3Urologie & Urologische Onkologie, Medizinische Hochschule Hannover,

Hannover

Purpose: Carboplatin plus docetaxel (CD) may be eective in mDRPC.

Platinum(II)-complexes interfere with steroid biosynthesis lowering tes-

tosterone levels. In this study, the impact of CD on free and total testos-

terone (fT, TT) serum levels and the prognostic role of fT and TT were

analyzed in mPC patients.

Methods: Docetaxel failure/resistance was dened according to the Pros-

tate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted

of at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 every 4

weeks (q4w), docetaxel (35 mg/m2) iv for one hour on days 1, 8, (15)

plus prednisone 2x5mg/day orally aer receiving informed consent until

disease progression or occurrence of intolerable adverse eects. Ecacy

measures were done following PCWG2 recommendations.

Results: Of the 118 pts. treated since February 2005, 95.8% had bone,

47.5% lymph node, 28.0% liver and 20.3% lung metastases. At the time

of the current analysis, the median follow-up time was 14.4 months. e

objective response rate (ORR) was 46.4% in the 69 pts. with measureable

disease (58.5%). Response of prostate-specic antigen (PSAR ≥ 50%) was

observed in 56 (47.9%) patients. Median progression free survival (PFS)

was 7.6 months (CI 95% 6.0, 9.1) and median overall survival (OS) was

15.7 months (CI 95% 12.2, 19.2). e most common reversible grade 3/4

toxicity was leukopenia/ neutropenia (36.4/28.8%). Median FT serum

levels were 0.35 pg/mL before and < 0.18 pg/mL during CD treatment

(nadir levels, p < 0.001; detection limit < 0.18 pg/mL). In multivariate

analyses, LDH>2xULN, PSAR≥50% and FT nadir levels below the

detection limit (< 0.18 pg/mL) during CD treatment were associated with

longer PFS (p < 0.05).

Conclusions: ese data suggest that CD may be an important salvage

treatment option for DRPC patients by inhibition of the testosterone bio-

synthesis.

Disclosure Statement: e authors declare no potential conicts of interest.

727

A Phase 3, Randomized, Open-Label, Multicenter,

Global Study of Ecacy and Safety of Durvalumab in

Combinationwith Gemcitabine+CiSPLATiN (G+C) for

Neoadjuvant Treatment Followed By Durvalumab Alone for

Adjuvant Treatment in Muscle-Invasive Bladder Cancer (MiBC)

(NiAGARA)

Hubert Rudolf Kübler 1; Thomas Powles 2; Joshua J Meeks 3;

MatthewGalsky 4; Michel S. van der Heijden 5; Hiroyuki Nishiyama 6;

HikmatAl-Ahmadie 7; Ashok Gupta 8; Jiabu Ye 9; Sarah Donegan 10;

DanaGhiorghiu 11; Salvatore Ferro 12; James Catto 13

1Uniklinikum Würzburg, Klinik und Poliklinik für Urologie und Kinderurologie,

Würzburg, Deutschland

2Queen Mary University of London, Barts Cancer Institute, London, United

Kingdom

3Northwestern University, Northwestern Medicine, Chicago Illinois , United

States

4The Mount Sinai Hospital, Hematology and Oncology faculty, New York,

United States

5Netherlands Cancer Institute, Molecular Carcinogenesis Division, Amsterdam,

Niederlande

6University of Tsukuba , Department of Urology, Ibaraki , Japan

7Memorian Sloan Kettering Cancer center, The David Solit Lab, New York ,

United States

8Astrazeneca, Immuno-Oncology , Gaithersburg, United States

9Astrazeneca, Biostatistic , Washington DC, United States

10Astrazeneca, Medical Scientist Immuno-Oncology, Washington DC, United

States

11Astrazeneca, Global Clinical Lead, Cambridge, United Kingdom

12Astrazeneca, Global Study, Gaithersburg, United States

13The University of Sheeld , Department of Oncology & Metabolism, Sheeld,

United Kingdom

Purpose: In the management of MIBC, neoadjuvant cisplatin-based com-

bination chemotherapy has demonstrated improved pathologic complete

response (pCR), event-free survival (EFS), and OS compared with rad-

ical cystectomy alone. Many patients still develop recurrence, including

progression to metastasis. e combination of chemotherapy and immu-

notherapy in a neoadjuvant setting and consolidating response post-cys-

tectomy in the adjuvant setting may improve clinical outcomes. PD-L1

inhibition with durvalumab, in combination with a standard neoadjuvant

regimen (G+C), may improve immune-mediated antitumor response and

increase the rates of pathologic responses and long-term survival.

Methods: NIAGARA is a Phase 3, randomized, open-label, multicenter,

global study (~1050 patients) with 1:1 randomization to durvalumab and

G+C combination (Arm 1) or G+C (Arm 2) as neoadjuvant chemother-

apy prior to radical cystectomy. Following radical cystectomy and during

adjuvant therapy, patients in Arm 1 will receive durvalumab monother-

apy for 8 cycles; patients in Arm 2 will receive no adjuvant treatment.

Patients with resectable MIBC (clinical stage T2N0M0-T4aN0M0) with

transitional cell histology planning to undergo a radical cystectomy will

be included. Primary endpoints are pCR rates at time of cystectomy fol-

lowing neoadjuvant treatment and EFS. Secondary and exploratory end-

points include proportion of patients who achieve pathologic response

<P2 (stages Pa, P1, and CIS) at time of cystectomy following neoadjuvant

treatment, EFS at 24 months, metastasis-free survival, proportion of pa-

tients who undergo cystectomy, and OS at 5 years. Enrollment opened in

Dec 2018.Clinical trial information: NCT03732677.

Results: Not yet available.

Conclusions: Not yet available.

References:

1. Iyer G and Rosenberg JE. Ann Oncol. 2018;29:2302-2312.

2. Abufaraj M, et al. Transl Androl Urol. 2016;5:735-744.

3. Dimitriadis I and Bamiais A. Eur Oncol Haematol. 2017;13:134-138.1

Disclosure Statement: Funded by AstraZeneca.

DE-21760/19

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787

Comparison of Online Information About Prostatectomy,

Radiotherapy and High-Intensity Focused Ultrasound for

Prostate Cancer Patients

Alexander Rühle 1; Thorben Hölscher 2; Lukas Käsmann 3

1University Hospital Freiburg, Department of Radiation Oncology, Freiburg,

Deutschland

2University Cologne, Faculty of Medicine, Deutschland

3University Hospital, LMU Munich, Department of Radiation Oncology,

Deutschland

Purpose: While the importance of the Internet as information source for

prostate cancer patients is increasing, there is little knowledge about the

relation between the prostate cancer treatment modality and the website’s

quality, readability and popularity.

Methods: By using the search engine Google, an Internet search for the

English terms “prostate cancer prostatectomy”, “prostate cancer radiother-

apy” and “prostate cancer hifu” as well as for the corresponding German

terms “Prostatakrebs Prostatektomie”, “Prostatakrebs Strahlentherapie”

and “Prostatakrebs HIFU” was conducted. e website’s quality of the

rst 30 search results was assessed by validated instruments such as the

DISCERN Plus score, the JAMA benchmark criteria and the Health on

the Net Code of Conduct (HONcode) certication. e readability of the

websites was analyzed with the Flesch-Reading-Ease, and the average us-

age time was assessed using Alexa Internet.

Results: Regarding the DISCERN Plus instrument and JAMA benchmark

criteria, the website’s quality was moderate with no dierences between

English and German websites. Using the JAMA benchmark criteria, the

quality of German radiotherapy websites was signicantly increased com-

pared to German HIFU websites. Similarly, there were signicantly more

websites with HONcode certication in the German radiotherapy group

than in the HIFU group; however, the majority of websites exhibited no

HONcode certication. Based on the Flesch-Reading-Ease, both English

and German websites were dicult to read with no dierences between

the surgery, radiotherapy and HIFU group. Likewise, the average user

time did not dier among the groups.

Conclusions: As the overall quality of the investigated websites is mod-

erate, the internet may be helpful in the treatment decision process of

prostate cancer patients. However, regarding the insucient readability

of many websites, a signicant number of patients have diculties to ob-

tain the relevant information highlighting the importance of high-quality

medical consultations by physicians.

832

A Prospective Phase 2A Study of Focal HDR Brachytherapy

for Low to Intermediate Prostate Cancer - Profocal

Peter Hass 1; Frank Fischbach 2; Daniel Schindele 3; Katharina Fischbach 4;

Martin Schostak 3; Maciej Pech 2; Thomas Brunner 5

1University Hospitals Magdeburg, Dept. of Radiation Oncology, Deutschland

2University Hospitals Magdeburg, Department of Diagnostic and Interventional

Radiology, Magdeburg, Deutschland

3University Hospitals Magdeburg, Department of Urology, Magdeburg,

Deutschland

2University Hospitals Magdeburg, Department of Diagnostic and Interventional

Radiology, Magdeburg, Deutschland

5University Hospitals Magdeburg, Dept. of Radiation Oncology, Magdeburg,

Deutschland

Purpose: An interim report on the feasibility of the technique and results

on tolerability and PSA course.

Methods: Single fraction interstitial HDR brachytherapy was performed

in patients with biopsy proven low to intermediate risk prostate cancer

(PC) of 1 lesion with an encompassing dose of ≥20Gy. Catheters were

placed into the lesions in a 3T-MRI system in local anesthesia. Follow up

was planned for PSA levels aer 3, 6, 12 and 24 months, a multiparamet-

ric (mp) MRI examination aer 6, 12 and 24 months and a re-biopsy 12

months aer HDR brachytherapy.

Results: e rst 9 patients with a follow-up for 6 months had tumors

exclusively located in the anterior part of the prostate mostly in the apical

region. Overall procedure time was 52 min and actual intervention time

34 min for the placement of the catheters. Median time of radiotherapy

was 8.3 min. Median encompassing dose was 27.4 Gy, median dose to

2 mL of rectum and bladder were 4.9 Gy and 8.5 Gy respectively. Using

the VAS scale the pain reported for the intervention ranged from 2 to 3.

No other complications were reported except for mild hematuria the day

aer the procedure in one patient. Short term follow up of at least six

months demonstrated no acute genitourinary or gastrointestinal toxicity.

Despite of the absence of antibiotic prophylaxis none of the patients

developed post-interventional signs of infection. PSA levels in all patients

decreased signicantly (from 8,9 to 1,7ng/ml on average). No residual or

recurrent prostate carcinoma was imaged at follow-up multi-parametric

MRI. Imaging results were conrmed by transrectal ultrasound (TRUS)

guided biopsies (n=4/9) showing no residual or recurrent prostate

carcinoma in the treated region at 12 months aer therapy.

Conclusions: HDR brachytherapy for localized PC is feasible and safe.

Catheters can be placed accurately and maximum therapeutic dose distri-

bution can be restricted to the tumour, no general anesthesia or antibiosis

is necessary.

851

Surgical Treatment of Synchronous and Metachronous

Metastatic Adrenal Tumors in Patients with Renal Cell

Carcinoma

Avetik Muradyan; Andrey Kostin; Nikolai Vorobyev; Hewad Taraki;

Aleksander Tolkachev

P. A. Hertsen Moscow Oncology Research Center - branch of FSBI NMRRC of

the Ministry of Health of Russia, Urological oncology department, Moscow,

Russland

Purpose: A comparative analysis of surgical treatment results in patients

with synchronous and metachronous solitary metastatic adrenal tumors

renal cell carcinoma origin.

Methods: Between 1997 and 2018, 93 patients (66 men and 27 women;

median age 60 years (28-78)) underwent surgical treatment, 58 patients

underwent simultaneous surgery for synchronous metastasis in the ad-

renal gland, and 35 patients underwent adrenalectomy due to a solitary

metachronous lesion.

Results: e sensitivity of ultrasound in the diagnosis of adrenal tumors is

80.6%, and computed tomography - 93.5%. Adrenal biopsy was successful

in 73.9%. Progression free survival (adrenal metastasis) aer the previous

primary surgical treatment was 44 months (5-204). During surgical treat-

ment of metachronous metastases, a decrease in the volume of blood loss

(p = 0.006), the average length of stay (p <0.0001), and the frequency of

postoperative complications (p = 0.022) were observed. During pathology

report study, clear cell RCC was observed in 84.9% (n = 79), papillary in

9.7% (n = 9), chromophobe in 2.2% (n = 2), and Collecting duct carcino-

ma (Bellini) in 3.2 % (n = 3).

e median follow up time was 42.0 ± 13.4 months (in the synchronous

lesion group - 24.0 ± 5.4 months, the median in the metachronous lesion

group was not achieved). e one-year survival of patients with a meta-

chronous lesion of adrenal was 82.3 ± 76.6% versus 52.8 ± 7.1% in the

synchronous lesion group, three-year survival was 79.2 ± 7.0% versus 32.3

± 7.6% and ve-year - 57.0 ± 10.0% versus 16.2 ± 12.0%. Metachronous

adrenal lesion (p <0.0001) and time to metastasis ≥24 months (p = 0.007)

were favorable prognosis factors. In a multivariate analysis, only a meta-

chronous lesion aected survival (p = 0.002).

Conclusions: Performing adrenalectomy among patients with a solitary

metachronous lesion can improve OS and PFS.

Disclosure Statement: no conict of interest

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2018

Geriatric Oncology

Poster

369

Changes in Survival Rates and Tumor Characteristics with

Increasing Age: Results from Population-Based Cancer

Registries

Klaus Kraywinkel 1; Birgitt van Oorschot 2; Julia Fiebig 1; Ulrich Wedding 3

1Robert Koch-Institut, Zentrum für Krebsregisterdaten, Berlin, Deutschland

2Universitätsklinikum Würzburg, Interdisziplinäres Zentrum für Palliativmedizin

an der Klinik und Poliklinik für Strahlentherapie, Würzburg, Deutschland

3Universitätsklinikum Jena, Abteilung für Palliativmedizin, Jena

Purpose: A high proportion of cancers aect individuals of older age, for

whom guidelines are applicable only to a limited extent due to comorbid-

ities or other factors. It has frequently been shown that cancer survival

rates are considerably lower for patients aged 75 and older, even when

taking age related life expectancy into account (relative survival). Still,

little is known about how these results evolve with advancing age and if

they correspond to changes in tumor characteristics. We therefore investi-

gated how relative survival rates, distribution of tumor stage and grading

change with advancing age for selected common cancers. In addition, we

examined the use of adjuvant chemotherapy in stage III colorectal cancer

according to age and sex.

Methods: Analyses were based on data from German population-based

cancer registries for the period 2012–2016, including patients aged 60

years or older with cancer of the bowel, bladder, lung, stomach, prostate

or breast as well as mature B-cell neoplasms. All results were calculated by

tumor site, sex and 5-year age groups (60-64 to 90+ years).

Results: Although the relative survival rates for all investigated entities

decreased continuously, particularly in the age groups from 65–69 to 85–

89 years, the results were inconsistent in terms the distribution of tumor

stages and grading: invasive bladder cancer showed a trend toward earlier

stages with increasing age, while the proportion of poorly dierentiated

tumors in gastric and lung cancer decreased. e proportion of adjuvant

chemotherapies for colorectal cancer with lymph node involvement re-

corded in the registries declined signicantly, particularly aer the age

of 75.

Conclusion Overall, the drop in relative survival rates with advancing age

cannot be explained by changes in tumor characteristics alone. Less ag-

gressive treatment strategies due to a higher prevalence of comorbidities,

dierent patient preferences and lower degrees of scientic evidence are

likely to have an inuence on these results.

Disclosure Statement: No conlict of interest

503

TrainIng Programs Promoting Daily Activity and Physical

Function of Older Patients with Cancer – a Questionnaire

Based Survey Regarding Individual Needs and Preferences

Stephanie Witte 1; Daniel Medenwald 2; Andre Golla 3; Eni Shehu 1;

DirkVordermark 2; Patrick Michl 4; Masha Binder 5; Joern Ruessel 6;

AnkeSteckelberg 1; Heike Schmidt 1

1UKH Institut für Gesundheits- und Pegewissenschaft, Halle (Saale),

Deutschland

2Universitätsklinikum Halle Universitätsklinik und Poliklinik für Strahlentherapie,

Halle (Saale), Deutschland

3Institut für Rahabilitationsmedizin , Halle (Saale), Deutschland

4UKH Universitätsklinik und Poliklinik für Innere Medizin I, Halle (Saale),

Deutschland

5UKH Universitätsklinik und Poliklinik für Innere Medizin IV, Halle (Saale),

Deutschland

6Carl-von-Basedow-Klinikum Saalekreis Medizinische Klinik II, Merseburg,

Deutschland

Purpose: Physical function of older patients with cancer oen decreases

during cancer therapy. is study aims to explore individual needs and

preferences of older patients with cancer in order to promote their phys-

ical activity (PA.)

Methods: e study is designed as a multi-center questionnaire-based

survey including a convenience sample of patients aged ≥ 60; ≥70 and

≥80 years with heterogeneous cancer diagnoses and stages; either receiv-

ing therapy or aer care. e questionnaire covers: gender; age; diagnosis

and life situation; previous and recent PA; changes of PA due to the cancer

diagnosis; individual goals for exercising; preferred type of PA; preferred

physical and social environment for exercising (e.g. individual training vs.

group based; home based vs. sport-center); aspects of motivation; need

for support; self-ecacy and the use of digital media. Data are analyzed

descriptively.

Results: In four centers 64 patients with a mean age of 69 ± 6.4 years; n=34

male; participated. e main cancer sites were hematological (n=17); lung

(n=9); breast (n=8) and pancreas (n=7). Patients stated their interest in

exercising to improve their mobility and physical performance (n=38) to

prevent falls (n=26); to relax (n=15) and reduce fatigue (n=14). Patients

preferred outdoors activities e.g. walking (n=48); cycling (n=38) and

gymnastics either at home (n=36); in a group (n=26) or with a partner

providing motivational support (n=23). For independent exercises at

home; personalized recommendations and instructions (paper-based

or video-based) were considered helpful (n=40). Digital media are used

regularly (n=31) or sometime by (n=12) patients.

Conclusions: e study provides useful insights into preferences; needs

and motivational factors for PA in older patients with cancer. Digital me-

dia seem to be feasible to reach this target group.To improve representa-

tiveness; the survey is currently expanded to n=280 participants including

three more oncological centres.

Disclosure Statement: e authors do not have any conicts of interest relevant to

the topic to declare.

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2018

599

Development of a Multimodal Supportive Intervention to

Promote Physical Functioning of Older Patients with Cancer

Eni Shehu 1; Sigrid Roggendorf 1; André Golla 2; Gundula Hübner 3;

GabrieleStangl 4; Andreas Lau 5; Andrea Diestelhorst 6; Dirk Vordermark 6;

Anke Steckelberg 1; Heike Schmidt 1, 6

1Institut für Gesundheits- und Pegewissenschaft, Medizinische Fakultät der

Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

2Institut für Rehabilitationsmedizin, Medizinische Fakultät der Martin-Luther-

Universität Halle-Wittenberg, Halle (Saale), Deutschland

3Institut für Psychologie, Martin-Luther-Universität Halle-Wittenberg, Halle

(Saale), Deutschland

4Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität

Halle-Wittenberg, Halle (Saale), Deutschland

5Institut für Sportwissenschaft, Martin-Luther-Universität Halle-Wittenberg,

Halle (Saale), Deutschland

6Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle (Saale),

Halle (Saale), Deutschland

Purpose: Physical function (PF) of older patients with cancer may decline

during therapy and endanger selfcare, independence and health related

quality of life (HRQOL). To prevent deterioration of PF and maintain

independence, targeted strategies considering the heterogeneity of older

people are needed. is study aims to develop and evaluate a multimod-

al supportive intervention to maintain PF and nutritional status of older

cancer patients undergoing outpatient radiotherapy.

Methods: e approach is based on the UK MRC Framework for the

development and evaluation of complex interventions involving clinical

experts and cancer survivors aged >60 years in development and pretest.

Assessments: comprehensive geriatric assessment, objective and subjec-

tive assessments of PF, nutrition, HRQOL, specic needs, goals, individ-

ual barriers and facilitators. Subsequent pilot-testing will be accessible

via digital media or paper based to examine which mode results in better

motivation and adherence.

Results: Each patient will receive tailored exercise and nutritional recom-

mendations according to his/her baseline assessments’ results. Pretest in-

cluding exercising and focus group interviews indicates feasibility and po-

tential usefulness of the exercises for maintaining everyday-functionality.

Participants appreciated the exibility of the programme, which includes

exercises in sitting and standing position. ey reported having stopped

rehabilitation classes since these were too strenuous. ey valued coor-

dination and balance exercises for increasing condence and preventing

falls. Participants rated their relatives’ help as a cornerstone for overcom-

ing their weaker self.

Conclusions: ere is a need in this target group for individually tailored

exercises that can be implemented in everyday life. e home-based inter-

vention comprises feasible exercises relevant for everyday functioning ad-

dressing endurance, coordination, balance and ne motor skills in sitting

or standing positions and nutritive advice.

Disclosure Statement: No conicts of interest

612

Social Relations of Older Patients with Cancer - Development

During the Disease Trajectory. A Retrospective, Qualitative

Study

Sigrid Roggendorf 1; Sven Weise 2; Patrick Michl 3; Dirk Vordermark 4;

OliverArránz Becker 5; Anke Steckelberg 1; Heike Schmidt 1, 4

1Institut für Gesundheits- und Pegewissenschaft, Medizinische Fakultät der

Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

2Sachsen-Anhaltische Krebsgesellschaft e.V., Halle (Saale), Deutschland

3Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Innere

Medizin I, Medizinische Fakultät der Martin-Luther-Universität

Halle-Wittenberg, Halle (Saale), Deutschland

4Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für

Strahlentherapie, Medizinische Fakultät der Martin-Luther-Universität

Halle-Wittenberg, Halle (Saale), Deutschland

5Institut für Soziologie, Martin-Luther-Universität Halle-Wittenberg, Halle

(Saale), Deutschland

Purpose: Social support is a domain of the geriatric assessment. However,

little is known about the development of social relationships during the

course of the disease, especially among older people with cancer. e aim

of this study was to explore the experiences of older patients with cancer

regarding the development of their social relationships during disease

trajectory.

Methods: A qualitative retrospective approach was chosen. People with

cancer aged ≥65 years at diagnosis, at least 6 months aer treatment were

interviewed using a semi-structured interview guide and asked to depict

their social relations at four given time points using the Family Board a

non-verbal method to visualize social relations. e audiotaped interviews

were transcribed, the Family Board constellations were documented and

qualitative content analysis was conducted. Ethical approval was obtained.

Results: Six women and four men (mean age: 74.5 years) participated. e

tumor sites were prostate, gastric, pancreas, esophagus, lymphatic glands,

and brain. Analyses revealed that all participants experienced changes in

their social network. Disease-related reduction of physical function was

experienced to lead to the loss of social and role function. Grandchildren

were perceived as supporting the ghting spirit and the return to every-

day life. Comparisons of the Family Board constellations showed growing

closeness of familial relations especially during treatment which remained

later on. Frequent changes in number, closeness or distance related to oth-

er non-family ties. Participants valued these ties as another important

source of emotional and instrumental support.

Conclusions: Findings underline the importance of repeated assessments

of social relations and the availability of social support. e Family Board

was well accepted and provided useful additional information especially

regarding the perceived development of social relations.

Disclosure Statement: No conicts of interest.

618

Supportive Needs and Burden of Older Patients with Cancer

and their Spouses- a Qualitative Analysis of Semi-Structured

Interviews

Marlene Dieke 1, 2; Anke Steckelberg 2; Patrick Michl 3; Dirk Vordermark 4;

Heike Schmidt 2, 4

1Universitätsklinik und Poliklinik für Pädiatrie II, Universitätsklinikum Halle

(Saale), Halle (Saale), Deutschland

2Institut für Gesundheits-und Pegewissenschaft, Medizinische Fakultät der

Martin-Luther Universität Halle-Wittenberg, Halle, Deutschland

3Universitätsklinik und Poliklinik für Innere Medizin I, Universitätsklinikum Halle

(Saale), Halle (Saale), Deutschland

4Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum

Halle (Saale), Halle (Saale), Deutschland

Purpose: Cancer and cancer therapy may cause burden of illness for pa-

tients and spouses likewise. is study aimed to explore needs and burden

of older cancer patients and their spouses during the disease trajectory.

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Methods: Within a qualitative retrospective design with semi-structured

interviews experiences of patients and their partners were explored. Pa-

tients 65 years and older having completed therapy and their partners

(dyads) were eligible. e interview transcripts were analyzed according

to qualitative content analysis (Mayring).

Results: Nine dyads were included. Mean age of patients was 74 years, of

partners 73 years, main tumor sites were: prostate (n=4), gastrointestinal

(n=3), breast (n=2). Patients were treated with: operation (n=10), chemo-

therapy (n=4) and radiotherapy (n=6), the most frequent comorbidity was

hypertension (n=9). Data analysis revealed positive and negative experi-

ences regarding 6 main themes: 1. Information of patients and partners

about illness and treatment: “My husband is still grateful. e doctor took

his time to explain everything.” 2. Empathic communication: “Tell your

wife: Sex is over”, 3. Trans-sectoral care: “I got discharged and did not

know what to do“, 4. Burden of illness regarding symptoms, side eects or

late eects (e.g. fatigue, impotence, incontinence): “Everything is dierent

than before, I got weaker, 5. Eects of illness and therapy on partnership

and sexuality including emotional burden and supportive needs of part-

ners: “it was not easy, I missed it (sexuality), there was a big gap, 6. Dyadic

coping: “my wife always backed me, she endured more than I can think

of”, “I worry about him (partner with cancer), but I do not talk about my

feelings because I do not want to burden him”.

Conclusions: e importance of empathic communication, information,

participation in decision making, the need for support regarding dyadic

coping and issues of intimacy and sexuality became evident. Due to the

qualitative design, these ndings should be examined in further studies.

Disclosure Statement: No conicts of interest

706

Meaningfulness of a Biological Marker (Advanced Glycation

Endproducts) Measured By Noninvasive Skin-Scan

(Autouorescence Measurement) in Geriatric-Oncological

Patients

Johannes Horn 1; Gabriele Meyer 2; Heike Schmidt 2; Franziska Flessner 2, 3;

Andreas Simm 4

1Institutes of Medical Epidemiology, Biometrics and Informatics, Medical

Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Deutschland

2Institute for Health and Nursing Science, Medical Faculty of Martin Luther

University Halle-Wittenberg, Halle (Saale), Deutschland

3Hautarztpraxis Prof.Dr. Khusru Asadullah, Potsdam, Deutschland

4Cardiac Surgery, University Hospital Halle (Saale), Halle (Saale), Deutschland

Purpose: Older patients with cancer dier regarding their biological

age, functionality, organ reserve and comorbidities. erefore, a compre-

hensive geriatric assessment (CGA) e.g. to assess physical and cognitive

functioning, nutritionals status, mood, self-care and social support is

recommended before planning oncological therapies1. In addition, a val-

id assessment of the biological age could add valuable information. To

investigate the possible benet of the autouorescence measurement of

advanced glycation endproducts in the skin (AGE value) in the clinical

context of geriatric oncology.

Methods: e Analysis of AGE data of a heterogeneous sample of older

cancer patients to generate hypotheses regarding the clinical relevance

of AGE. e AGE value of the skin was determined by autouorescence

measurement in n=100 cancer patients. Based on of age-specic refer-

ence values, AGE values were categorized as age-appropriate or pre-aged.

Descriptive analyses regarding sex, comorbidities, cancer diagnoses and

results of geriatric assessments were performed. To explore the predictive

properties of AGE values survival data were analyzed with simple Ka-

plan-Meier estimates and Cox regressions with log-rank tests.

Results: e analyses of the AGE values were performed on 97 patients

(47 women and 50 men) with a mean age of 75 ±5 years. Main cancer

sites comprised lung n = 27 (28%), hematological n = 16 (17%), breast

n = 14 (14%), head/neck n= 14 (14%), skin n = 12 (13%) and other =14

(14%). AGE values were Ø 3.1 Arbitrary Units (AU) ±0.8 (min. 1.7, max.

6.1). According to the age-specic reference values n =38 patients were

categorized as age-appropriate and n =59 as the pre-aged. e survival

time analyses indicated a survival advantage for tumor patients with high

AGE values (p = 0.036, KI =1.038- 2.937, n = 97).

Conclusions: Due to the exploratory design, the results are not general-

izable. To the best of our knowledge the result that high AGE value were

associated with a better survival of older cancer patients have so far not

been puplished elsewhere.

Reference:

1. Schmidt et al. 2017.

861

How to Deal with Senescent Patients in the Field of Visceral

Surgery?

Hans-Michael Tautenhahn 1, 2; Felix Dondorf 1; Philipp Felgendre 1, 2;

Astrid Bauschke 1; Uta Dahmen 1; Falk Rauchfuss 1; Utz Settmacher 1

1Clinics of General, Visceral and Vascular Surgery, University Hospital Jena,

Jena, Deutschland

2Research Programme „Else Kröner-Forschungskolleg AntiAge“, University

Hospital Jena, Jena, Deutschland

Purpose: Senescence is considered a risk factor for surgery. Due to a lack

of scientic evidence, therapeutic decisions are oen based on the clini-

cal experience of the individual surgeon. e Center of Geronto-Surgery

uringia was founded to improve the outcome aer surgery for this

growing group of patients at risk. To better characterize the age-depen-

dent risk prole, we performed a retrospective analysis of the in-hospital

results aer visceral surgery performed in the last 5 years (y).

Methods: Using the clinic patient information system data from patients

being treated in our department were extracted. Out of this cohort two

groups were formed containing either patients below the age of 35y or

older than 65y of age. Using an Access database all clinically relevant pa-

rameters (e.g. age, sex, comorbidities, duration of hospital stay, complica-

tion rate…) were assembled. Statistical analyses were performed using R.

Results: e total number of patient older than 65y as well as in relation

to the cohort of patients below 35y was rising signicantly in the study

period. Geriatric surgery patients more oen suering from postoperative

complications such as cardiovascular, pulmonary or neurological com-

plications. Even the morbidity rate was signicantly higher in the older

patient cohort, no dierence was detected in the mortality rate (30days

post-operative). e length of hospital stay was signicantly longer in the

geriatric patients.

Conclusions: Facing the problem of an ageing population yet no solu-

tions are available for this complex patient cohort especially in surgery

manners. Keeping in mind the elevated postoperative morbidity avoiding

a higher postoperative mortality is one of the challenging problems in the

eld of geriatric surgery. In our mind it is ethically not feasible to refuse

an operation in elderly patients in principle. On the other hand; these el-

derly patients are in need for an individual pre-; peri- and postoperative

course. e formation of geriatric surgery units is one promising way to

treat these patients optimized.

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2018

Gynecological Cancer

Best-of-Abstracts-Vorträge

523

Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab

(CD-Bev) vs. Carboplatin/Gemcitabine/Bevacizumab (CG-BEV)

in Patients with Recurrent Ovarian Cancer: a Prospective

Randomized Phase iii Engot/GCiG-Intergroup Study (Ago

Study Group, Ago-AUSTRiA, ANZGOG,GiNECO, SGCTG)

Lars Hanker 1; Philipp Harter 2; Jalid Sehouli 3; Jörn Rau 4; Ulrich Canzler 5;

Barbara Schmalfeldt 6; Falk Thiel 7; Ahmed El-Balat 8; Frederik Marmé 9;

Nikolaus De Gregorio 10; Klaus Baumann 11; Sven Mahner 12;

Werner Meier 13; Tjoung-Won Park-Simon 14; Eva-Maria Grischke 15;

Peter Hillemanns 14; Felix Hilpert 16; Hans-Joachim Lück 17; Rainer Kimmig 18;

Martina Gropp-Meier 19; Alexander Burges 12; Christian Jackisch 20;

Willibald Schröder 21; Jacobus Psterer 22

1Universitätsfrauenklinik Lübeck; 2Klinikum Essen Mitte

3Charite Berlin; 4KKS Marburg

5Universitätsfrauenklinik Technische Universität Dresden

6Universitätsfrauenklinik Hamburg Eppendorf

7Universitätsfrauenklinik Erlangen

8Universitätsfrauenklinik Frankfurt

9Universitätsfrauenklinik Heidelberg

10Universitätsfrauenklinik Ulm

11Klinikum der Stadt Ludwigshafen am Rhein

12Universitätsfrauenklinik München Großhadern

13Evangelisches Krankenhaus Düsseldorf

14Medizinische Hochschule Hannover

15Universitätsfrauenklinik Tübingen

16Universitätsfrauenklinik Kiel

17Gynäkologisch Onkologische Praxis Hannover

18Universitätsfrauenklinik Essen

19KH St. Elisabeth Ravensburg

20Sana Klinikum Oenbach

21Onkologikum Bremen

22Zentrum für Gynäkologische Onkologie Kiel

Purpose: In patients with recurrent ovarian cancer (ROC) suitable for

platinum based retreatment (PBT) standard therapy comprises CG-BEV

and Carboplatin(C)/pegylated liposomal-Doxorubicin (D). CG-BEV sig-

nicantly increases progression-free-survival (PFS) over CG alone whilst

CD has one of the best therapeutic indices for ROC-PBT. e aim of this

trial was to evaluate whether CD is superior to CG when given in combi-

nation with BEV with investigator-determined PFS as primary objective.

Methods: Between 2013 and 2015 682 pts. with ROC-PBT were random-

ized to CG-BEV (n=337) or CD-BEV (n=345). Secondary objectives were

overall survival (OS), biological progression-free survival (PFSBIO) by

serum CA125, quality of life (QoL) assessed by EORTC-QLQ-C30 and

QLQ-OV28, safety and tolerability.

Results: Mean age was 61.1 (SD 10.3) years, 87.4% had serous histology, 83.1%

were high grade, 41.5% were pretreated with BEV as part of rst-line treatment.

CG-BEV was associated with 359 (53.3%) serious adverse events vs. 314 (46.7%)

for CD-BEV (p=0.083). Median PFS in the standard arm CG-BEV was 11.7

months (95% CI 11.1-12.8) vs. 13.3months (95% CI 11.7-14.3) in the arm CD-

BEV (HR 0.80; 95% CI 0.68-0.96, p=0.0128). Median OS in the standard arm

CG-BEV was 27.9 months (95% CI 25.6-30.3) vs. 32.0 months (95% CI 26.6-

34.9) for CD-BEV (HR 0.810; 95% CI 0.668-0.983, p=0.0319).

In the stratum with previous anti-angiogenic treatment (n=309) median

PFS was 10.1 months (95% CI 8.5-11.2) for CG-BEV vs. 11.3 months (95%

CI 10.1-13.8) for CD-BEV (HR 0.73; 95% CI 0.57-0.94, p=0.0126).

Conclusions: CD-BEV provided a signicant PFS improvement compared

to CG-BEV in patients with ROC suitable for PBT and resulted also in supe-

rior OS compared to CG-BEV. CD-BEV was associated with fewer serious

adverse events. e global Quality of life status was not worsened by CD-

BEV. us CD-BEV is a new standard of care for patients with ROC PBT.

Disclosure Statement: ere are no disclosures.

Vorträge

265

Prevalence of BRCA1 and BRCA2 Mutations in Patients with

Primary Epithelial Ovarian Cancer Based on Family History of

Breast and Ovarian Cancers using The German Checklist – a

Single Center Experience

Beyhan Ataseven 1, 2; Denise Tripon 1; Philipp Harter 1; Stephanie

Schneider 1; Kerstin Rhiem 3; Florian Heitz 1, 4; Sonia Prader 1; Thais Baert 1, 5;

Alexander Traut 1; Nina Pauly 1; Sarah Ehmann 1; Enzo Ricciardi 1;

Helmut Plett 1; Rita Katharina Schmutzler 3; Andreas du Bois 1

1Kliniken Essen-Mitte, Department of Gynecology and Gynecologic Oncology,

Essen, Deutschland

2LMU München, Department of Obstetrics and Gynecology, University Hospital,

München, Deutschland

3Uniklinik Köln, Center for Hereditary Breast and Ovarian Cancer, Center for

Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne,

Köln, Deutschland

4Charité – Universitätsmedizin Berlin, Department of Gynecology, Campus

Virchow Clinic, Charité Medical University, Berlin, Berlin, Deutschland

5Universität Leuten, Department of Oncology, Laboratory of Tumour

Immunology and Immunotherapy, ImmunOvar Research Group, KU Leuven,

Leuven, Belgien

Purpose: BRCA1/2 are the major susceptibility genes involved in heredi-

tary epithelial ovarian cancer (EOC). Genetic testing for EOC pts in Ger-

many was recommended if validated family history (FH) based criteria

were fullled that confer a probability of a pathogenic BRCA1/2 mutation

>10%. e German checklist (CL) is a scoring tool developed and further

validated by the consortium based FH criteria including type of cancer

and ages at diagnosis of a detailed 3-generation FH. In the past, pts with

EOC lacking a FH (singular EOC) were not classied at risk according

to the checklist. Since results of the AGO TR1-study revealed mutation

prevalences of >10% also in singular EOC patients irrespective of the fa-

milial predisposition, testing is now recommended in all pts with EOC

by the German S3 guideline. Our aim was to evaluate the prevalence of

BRCA1/2-mutation(s) by CL score.

Methods: Between 01/11-05/19 1206 primary EOC pts were treated at

Kliniken Essen-Mitte. A total of 537 patients were tested for BRCA1/2

only (cohort A), in 445 cases multigene testing (TruRisk® panel) including

non-BRCA genes was performed (cohort B). For each pts, the CL score

was evaluated based on personal and familial BC/OC history.

Results: In cohort A, 23.6% (127/537) of pts had a BRCA1 (n=92) or

BRCA2 (n=35) mutation. In cohort B, 6.2% (22/356) of the patients without

BRCA1/2-mutation had other mutation (RAD51C (6), BRIP1 (4), PALB2 (3),

MSH6 (2), RAD51D (2), others (5). In 40.6% (218/537) of the pts the CL score

was 2 (singular EOC). e prevalence for BRCA1/2 mutation in cohort A was

11.0%, 17.4%, 25.5%, 35.1%, 51.4%, and 66.7% for pts with CL score 2, 3, 4, 5,

6, and ≥7, respectively. e prevalence for total mutations in the panel testing

cohort B was 15.3%, 16.7%, 28.6%, 39.1%, 44.8%, and 62.5% for pts with CL

score 2, 3, 4, 5, 6, and ≥7, respectively.

Conclusions: e BRCA1/2 mutation prevalence in EOC pts positively

correlated with increasing CL scores. However, the prevalence of muta-

tion was >10% even in singular EOC cases conrming the necessity for

oering genetic panel testing independent of FH to all pts with EOC.

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Poster

211

Olaparib Routine Clinical Practice in Germany – Interim

Results of The Non-Interventional C-Patrol Study with a Focus

on Patients who Switched from The Olaparib Capsule to the

Tablet Formulation

Jacek P. Grabowski 2; Frederik Marmé 3; Felix Hilpert 4; Manfred Welslau 5;

Andreas Hartkopf 6; Ahmed El-Balat 7; Regina Glowik 8; Jalid Sehouli 9

1Universitätsmedizin Berlin Charité , Klinik für Gynäkologie, Campus Virchow

Klinikum, Berlin, Deutschland

1Universitätsmedizin Berlin Charité , Klinik für Gynäkologie, Campus Virchow

Klinikum, Berlin, Deutschland

3Universitätsklinikum Mannheim, Frauenklinik, Mannheim, Deutschland

4Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg ,

Deutschland

5Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaenburg,

Aschaenburg, Deutschland

6Universitäts-Frauenklinik Tübingen, Department für Frauengesundheit,

Tübingen, Deutschland

7Universitätsklinikum Frankfurt, Klinik für Frauenheilkunde und Geburtshilfe,

Frankfurt am Main, Deutschland

8AstraZeneca GmbH, Oncology, Wedel, Deutschland

9Universitätsmedizin Berlin Charité, Klinik für Gynäkologie mit Zentrum für

onkologische Chirurgie, Berlin, Deutschland

Purpose: Olaparib (50 mg hard capsules, HC) was the 1st PARP inhibitor

approved in the EU in 12/2014 as monotherapy for maintenance treat-

ment of adult patients (pts) with platinum-sensitive relapsed BRCA-mu-

tated ovarian cancer (PSR-OC) who are in response to platinum-based

chemotherapy. In addition, lm-coated tablets (FT, 100/150 mg) were ap-

proved in the EU in 05/2018 regardless of BRCA status. Here, we report

real-world olaparib treatment data from pts who switched from olaparib

HC to FT.

Methods: e German prospective, non-interventional study C-PATROL

collects real-world clinical and patient-reported data of pts treated with

olaparib according to label. Data of 255 pts were analyzed in this interim

analysis (data cut-o: 01 April 2019) using descriptive statistics.

Results: e most commonly used olaparib HC starting dose was 800 mg

(in 85% of pts with HC (n=177), and in 77% of pts who started on HC and

switched to FT (n=47)). Most pts who started olaparib FT maintenance

therapy (n=28) received an initial daily dose of 600 mg olaparib (89%).

At the switch from the capsule to the tablet formulation, most pts started

with a FT daily dose of 600 mg olaparib (68%). In the 3 subgroups (HC,

switcher, FT), the median treatment duration was 9, 17.4 and 2.9 months,

respectively. Adverse events (AEs) ≥ grade 3 occurred in 38% (HC), 32%

(switcher) and 18% (FT) of patients; and AEs leading to discontinuation

of olaparib therapy in 11% (HC), 0% (switcher) and 7% (FT).

Conclusions: is interim analysis provides rst RWE data for the switch

from olaparib capsule to tablet formulation. e data indicate that switch-

ing was well tolerated by pts under routine conditions. e observed

toxicity prole is in line with data from clinical trials and prior interim

analyses of this study with olaparib as maintenance therapy in PSR-OC

and primary advanced OC.

Disclosure Statement: Study funded by AstraZeneca

Frederik Marmé: honoraria received for speaker, consultancy or advisory role,

travel, from AstraZeneca, Tesaro, Roche, Novartis, Pzer, PharmaMar, Genomi-

cHealth, CureVac, Amgen, Eisai, MSD,Celgene, Clovis

Felix Hilpert: Honoraria: Astra Zeneca, Clovis, Roche, Tesaro, MSD, PharmaMar,

Pzer, Novartis

Advisory Board: AstraZeneca, Roche, Tesaro, Clovis, MSD, PharmaMar

Manfred Welslau: No conict of interest

Andreas Hartkopf: Andreas Hartkopf has received honoraria (speakers bureau and

consulting fees) from AstraZeneca, Eisai, GenomicHealth, Lilly, MSD, Novartis,

Pzer, Roche, Tesaro, Teva.

Ahmed El-Balat: Ahmed El-Balat: membership on advisory councils, speaker’s

activities for AstraZeneca, Roche, PharmaMar, Olympus

Regina Glowik: Angestellte der Firma AstraZeneca

Jalid Sehouli: J. Sehouli: Advisory and expert activities for PharmaMar, Clovis,

Tesaro, Roche, Roche Diagnostics, Astra Zeneca,Merck, Bayer,Eisei, Johnson

and Johnson, MSD, Novocure, Amgen, Lilly; Receipt of professional fees from

PharmaMar, Clovis, Tesaro, Roche,Astra Zeneca, receipt of research grant support

(institution) from PharmaMar, Clovis, Tesaro, Roche, Astra Zeneca, Medimmune,

Bristol Myers, Lilly.

360

G Protein-Coupled Estrogen Receptor (GPER-1) and Agonist

G-1 Inhibit Growth of Ovarian Cancer Cells by Activation of

Anti-Tumoral Transcriptome Responses

Susanne Schüler-Toprak; Oliver Treeck; Tanja Ignatov; Atanas Ignatov;

Olaf Ortmann

Regensburg, Department of Obstetrics and Gynecology, University Medical

Center Regensburg, Regensburg, Deutschland

Purpose: Previous studies addressing the role of G-protein coupled es-

trogen receptor (GPER-1) in ovarian cancer yielded contradictory results.

On the one hand, GPER-1 was suggested to act as tumor suppressor; on

the other hand, this receptor was reported to mediate oncogenic eects on

ovarian cancer cells in vitro and to predict poor survival of ovarian cancer

patients. e present in vitro study intended to further elucidate the role

of this receptor in ovarian cancer cells comparing the eects of a GPER-1

knockdown and treatment with its agonist G-1 on cell growth, apoptosis

and the transcriptome of two ovarian cancer cell lines.

Methods: GPER-1 expression in OVCAR-3 and OAW-42 ovarian cancer

cells was knocked down by RNAi. e eects on cell growth were mea-

sured by means of the uorimetric Cell Titer Blue assay and on the tran-

scriptome by Aymetrix GeneChip analysis.

Results: Knockdown of GPER-1 and treatment with its agonist G-1 ex-

erted converse eects on growth and the transcriptome of ovarian cancer

cells. GPER-1 knockdown resulted in a signicant growth stimulation

of both cell lines, with a maximum increase by 37% (OVCAR-3) or 28%

(OAW-42), (both p<0.01). In contrast, treatment with GPER-1 agonist

G-1 decreased growth of both cell lines in a dose-dependent manner, with

a maximum inhibitory eect of 1 µM of this drug of about 80% 6 days

aer treatment. To address the question of o-target actions of this high

G-1 concentration, we found both GPER-1-dependent and -independent

eects on the transcriptome. Generally, treatment with this drug led to

a transcriptome response associated with growth inhibition. In contrast,

knockdown of GPER-1 exerted opposite eects, stimulating pathways

activating mitosis, transcription and translation, but inhibiting pathways

associated with apoptosis or interferon signaling.

Conclusions: Our data suggest that GPER-1 is able to inhibit growth of

ovarian cancer cells and support the hypothesis that this gene acts as a tu-

mor suppressor. Further studies are required to examine the signicance

of our data in the in vivo situation.

371

Revised FIGO Classication for Cervical Carcinoma

2019 - What´s New and What are the Problematis Issues?

Lars-Christian Horn 1; Christine E. Brambs 2; Anne Kathrin Höhn 1

1Institut für Pathologie, Universitätsklinikum Leipzig AöR, L

2Frauenklinik des Klinikums rechts der Isar , Technische Universität, München,

Deutschland

Purpose: Numerous therapeutic and prognostic studies of cervical carci-

noma have made a revision of the FIGO classication necessary.

Methods: Evaluation of the new FIGO classication and comparison with

previous classication dated back on 2009 und with the current TNM

classication from 2017.

Results: For microinvasive carcinomas, the horizontal dimension is no

longer considered, and diagnosis and staging will solely be made by the

depth of cervical stromal invasion. Lymphovascular invasion beyond the

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deepest point of stromal inltration by tumor cells does not alter the stage.

ere will be a new subclassication of macroinvasive carcinoma conned

to the uterine cervix which will be made by largest tumor extension as

followed: FIGO IB1/T1b1: invasive carcinoma >0.5cm depth of stromal

invasion and <2cm in largest dimension, FIGO IBII/T1b2: invasive carci-

noma >2cm and <4cm, FIGO IBII/T1b3: invasive carcinoma >4cm. Pelvic

as well as para-aortic lymph nodes will be dened as regional nodes. Pel-

vic lymph node metastases only will be categorised as FIGO IIIC1/pN1a

and para-aortic lymph node involvement with or without concomitant

pelvic involvement will be FIGO IIIC2/pN1b. Uterine corpus as well as

adnexal involvement are disregarded for staging purpose as they does not

alter itself either the prognosis or the management at time.

Conclusions: the new denition of microinvasive carcinoma may result

in stage migration which impact treatment decisions. e same issue will

occur for the denition of regional lymph nodes. An open question is still

the classication of ovarian involvement.

Disclosure Statement: ere are no disclosures.

373

Mesonephric-Like Endometrial Carcinoma May Represent an

Aggressive Tumor with Characteristic KRAS-Mutation

Lars-Christian Horn; Tina Unger; Irene Krücken; Anne Kathrin Höhn

Institut für Pathologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland

Purpose: Very rarely mesonephric-like features are seen in ACs of the

endometrium and account for about 1% of all endometrial AC. Here we

report three cases with clinical, histopathological and molecular analyses.

Methods: Case description with immunohistochemical and molecular

analyses. Review of the literature of mesonephric-like AC of the endome-

trium for porgnosis.

Results: e mean age of the patients was 60.0 years (range range 31 to 91

years). Vaginal bleeding is the leading symptom. More than 50% showed

local advanced disease, i.e. >FIGO stage II, one third lymph node involve-

ment. About 10% of the patients died of the disease and 40.0% were alive

with evidence of the disease. Most common site of distant recurrent dis-

ease was pulmonary. Positive immunostaining of at least two of the meso-

nephric markers, like CD 10, GATA-3 and TTF with negative results for

ER and PR allows the correct diagnosis in line with mixed growth patterns

on H&E. Almost all cases represented KRAS-mutation at codon 12.

Conclusions: Uterine ML-AC are likely of Müllerian origin but represent

mesonephric features at the histopathologic, immunophenotypic and mo-

lecular level. e immunohistochemical panel of GATA-3, TTF-1, CD 10

(luminal staining), calretinin, p53 and p16 in addition to KRAS-mutation

allows the correct diagnosis of ML-AC in the majority of cases. ML-AC

may represent an aggressive subtype of endometrial cancer with pulmo-

nary involvement.

Disclosure Statement: ere are no disclosures.

417

The Use of miRNA in the Early Detection of Cervical

Intraepithelial Neoplasia

Leonore Weikert; Julia Wittenborn; Jochen Maurer; Elmar Stickeler

Uniklinik RWTH Aachen, Klinik für Gynäkologie und Geburtsmedizin, Aachen,

Deutschland

Purpose: Today, one of the biggest challenges in cancer therapy and

prevention is the latter, which includes the diculty to predict progression

of early lesions or pre-stages to invasive disease. In this context, the

characterization and categorization of pre-neoplastic lesions of squamous

cell carcinoma called cervical intraepithelial neoplasia (CIN) is an

important task.

Methods: Using small molecular markers extracted from cervical mucus

saves the patient the discomfort of a colposcopy with biopsies. We utilized

miRNAs extracted from cervical mucus samples from healthy patients

and patients with CIN 3 lesions.

Results: We can show that miRNA analysis from cervical mucus of 49 pa-

tients allowed us to distinguish between healthy patients and patients with

a CIN 3 lesion. e miRNA panel used in combination allowed for highly

signicant testing (p<0,0001) of CIN 3 status. In parallel, HPV status of

the patients, which is an important criteria for screening as well as treat-

ment strategies in the therapy of cervical cancer, signicantly correlated

with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-

143-3p, a subpanel of the original six miRNAs.

Conclusions: We provide here the rst proof-of-concept for a cervical

mucus-based testing for pre-neoplastic stages of cervical squamous cell

carcinoma.

Disclosure Statement: no conict of interest

423

Histotype-Specic Analysis of Acid Ceramidase Expression

in Ovarian Cancer

Ahmed El-Balat; Sven Becker

Uniklinikum Frankfurt am Main, Frankfurt am Main, Deutschland

Purpose: Acid ceramidase (ASAH1) is a key player in sphingolipid me-

tabolism and signalling. It has prognostic value for several cancers, but

histotype-specic analyses of ovarian cancer are not yet available.

Methods: We used three retrospective TMA cohorts encompassing a to-

tal of 1106 ovarian cancers with follow up data for immunohistochemical

analysis of acid ceramidase (ASAH1) expression. Patients with sub-opti-

mal debulking and persistent residual tumor aer surgery introduced bias

in the prognostic analysis and were excluded from further studies.

Results: Overall, we detected an association of ASAH1 expression with

improved prognosis in ovarian cancer patients. ASAH1 expression dif-

fered between histological ovarian cancer histotypes with most frequent

expression in endometrioid and clear cell ovarian cancer, which are both

associated with good prognosis. Stratied subgroup analyses within these

histotypes did not reveal signicant survival dierences, but the power of

the analysis may be limited by smaller sample sizes. In contrast to breast

cancer, we found only a modest concordance between estrogen receptor

status and ASAH1 expression within the endometrioid ovarian cancer

histotype. In an exploratory analysis of estrogen receptor negative endo-

metrioid ovarian cancer, ASAH1 expression was associated with signi-

cantly improved overall survival (P=0.007).

Conclusions: Acid ceramidase is most frequently expressed in endome-

trioid and clear cell histo-types and could add independent prognostic

value to estrogen receptor in endometrioid ovarian cancer. Modulating

sphingolipid metabolism may lead to novel therapeutic intervention strat-

egies for this disease.

Disclosure Statement: Nothing to disclose.

425

Claudin1 Expression in Border Line Epithelial Tumors

of the Ovary

Ahmed El-Balat; Sven Becker

Uniklinikum Frankfurt am Main, Frankfurt am Main, Deutschland

Purpose: To evaluate the integral transmembrane protein Claudin 1 as

marker for borderline ovarian tumors (BOTs).

Methods: We analyzed a retrospective cohort of 114 BOTs with vali-

dated diagnosis by an independent pathologist. Immunohistochemical

detection of Claudin 1 was quantied as combined immunoreactive score

blinded to clinical patient data. Analyses were performed for Claudin 1

positive versus negative.

Results: We detected Claudin 1 positivity in 26.3% of patients. ere

was no signicant correlation between the dierent histological subtypes

and Claudin 1 expression. e expression of Claudin1 was less frequent

in patients with FIGO Stage I (p<0.045). Claudin1 expression was more

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frequent in cases with micropapillary pattern (p=0.047) and was highly

associated with the presence of implants (p=0.003).

Conclusions: Our analysis links Claudin 1 with micropapillary pattern.

Positive expression is associated with the presence of implants, which is

related to elevated risk of recurrence. Accordingly, Claudin 1 is an inter-

esting marker and worth further analyses of its prognostic value in BOTs.

Disclosure Statement: Nothing to disclose.

478

Inuence of Lymph Node Status and Treatment Strategy

on Overall Survival in Advanced Cervical Cancer

Stella Knobloch 2; Thomas Papathemelis 3; Michael Gerken 2;

Anton Scharl 3; Michael Anapolski 4; Atanas Ignatov 1; Olaf Ortmann 1;

Elisabeth C. Inwald 1; Madeleine Hetterich 1; Sophia Scharl 5;

Monika Klinkhammer-Schalke 2

1Department of Obstetrics and Gynecology, University Medical Center

Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland

2Tumor Center, Institute for Quality Management and Health Services Research,

University of Regensburg, Regensburg, Deutschland

3Department of Obstetrics and Gynecology, Klinikum St. Marien Amberg,

Amberg, Deutschland

4Department of Obstetrics and Gynecology, University of Witten-Herdecke,

KKH Dormagen, Dormagen

5Department of Radiation Oncology and Radiotherapy in the Klinikum rechts

der Isar, Technische Universität München (TUM), München

Purpose: e lack of prognosis data hinders the implementation of an

optimal therapy for cervical cancer. Because surgery is associated with

higher morbidity, we examined the overall and relapse-free survival aer

various treatments in patients with cervical carcinoma in the FIGO stages

IIB, IIIA, IIIB and IVA with or without aected lymph nodes using data

from a clinical cancer registry in a retrospective cohort study.

Methods: Between 2002 and 2015, the Register of the Tumor Center Re-

gensburg documented 389 patients with cervical carcinoma in the FIGO

stages IIB, IIIA, IIIB and IVA. e results of the Kaplan-Meier analyzes

were given in 5-year survival and recurrence probabilities as well as the

median survival time. We estimated the hazard ratios for overall survival

aer various therapies with univariable and multivariable Cox regression

for risk adjustment.

Results: We have demonstrated the need for a thorough assessment of

lymph node status in order to obtain reliable data for the treatment strate-

gy. Our analysis showed signicant dierences in overall survival in FIGO

IIB as a function of therapy and nodal status. Overall survival was lower

with radiochemotherapy without surgery for patients with N0 compared

to a combination of surgery and chemoradiotherapy (HR = 3.012, 95%

CI 1.075 - 8.441, p = 0.036). However, in patients with aected lymph

nodes (N1), chemoradiation without surgery resulted in a comparable re-

sult (HR = 0.808, 95% CI 0.188 - 3.403, p = 0.765), while surgery alone

resulted in a poor outcome (HR = 2.889, 95% CI 1,356 - 6,156, p = 0.006).

Regardless of nodal status, advanced cervical cancer chemotherapy (FIGO

III) was superior to surgery.

Conclusions: Our study indicates that FIGO IIB patients with cervical

cancer benet from a combination of surgery and chemoradiotherapy for

long-term oncologic outcome. In the case of a lymph node involvement,

however, surgery did not result in improvement of overall survival. In pa-

tients with stage FIGO III disease chemotherapy shows the best results.

Disclosure Statement: e authors declare no conict of interest.

485

Is there an Advantage of Lymphadenectomy for Overall and

Recurrence-Free Survival in Endometrial Carcinoma Type

I FIGO IB G1-2? A Retrospective Population-Based Cohort

Analysis

Dunja Hassas 1; Thomas Papathemelis 2; Michael Gerken 1; Sophia Scharl 3;

Anton Scharl 2; Michael P. Lux 4; Mathias W. Beckmann 5; Olaf Ortmann 6;

Monika Klinkhammer-Schalke 1

1Tumor Center, Institute for Quality Management and Health Services Research,

University of Regensburg, Regensburg, Deutschland

2Department of Obstetrics and Gynecology, Klinikum St. Marien Amberg,

Amberg, Deutschland

3Department of Radiation Oncology and Radiotherapy in the Klinikum rechts

der Isar, Technische Universität München (TUM), München, Deutschland

4Frauen- und Kinderklinik St. Louise, Paderborn

5Gynecological University Cancer Center Franken, Gynecological Clinic,

University Hospital Erlangen, CCC Erlangen-EMN, Friedrich-Alexander University

Erlangen, Erlangen, Deutschland

6Department of Obstetrics and Gynecology, University Medical Center

Regensburg, Caritas Hospital St. Josef Regensburg, Regensburg, Deutschland

Purpose: e recommended therapy for patients with type I FIGO IB

endometrial carcinoma is hysterectomy and adnexectomy. However, the

therapeutic benets of additional pelvic and para-aortic lymph node dis-

section (LND) are still under discussion. In this study, we retrospectively

studied overall survival (OAS) and relapse-free survival (RFS) in patients

with endometrial carcinoma type I FIGO IB who have undergone a sys-

tematic or elective lymphadenectomy compared to patients without LND.

Methods: We included 299 patients from the registry database of the Re-

gensburg Tumor Center, who were diagnosed with endometrial adeno-

carcinoma of type I FIGO IB between 1998 and 2015. A multivariable

Cox regression was applied to the selected patient data and the hazard

ratios for OAS and RFS for the interventions performed were estimated.

Furthermore, we have made risk adjustments with respect to clinicopath-

ological parameters.

Results: We observed signicant benets of LND in univariable survival

without risk adjustment. However, we have not seen this eect conrmed

in the multivariable regression analysis aer risk adjustment. In this case,

the hazard ratio (HR) for OAS in patients without LND decreased to

1.214 (95% CI 0.771-1.911, p = 0.402) compared to patients with LND,

the HR for RFS to 1.059 (95% CI 0.689). 1.626, p = 0.795). Similarly, a

benet of systematic versus elective LND aer risk adjustment could not

be conrmed.

Conclusions: Contrary to previous observations in patients with high-

grade endometrial carcinoma, our study provides evidence that LND, and

in particular systematic lymphadenectomy, is not benecial in patients

with type I FIGO IB endometrial carcinoma in terms of overall and re-

currence-free survival.

Disclosure Statement: e authors declare no conict of interest.

491

Prognostic Factors and Outcomes of Cervical Cancer Patients

(2007-2016): a Population-Based Analysis

Miriam Rottmann; Gabriele Schubert-Fritschle; Jutta Engel

Tumorregister München (TRM), Bayerisches Krebsregister - Regionalzentrum

München (LGL), am Klinikum der Universität München, Institut für Medizinische

Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-

Maximilians-Universität (LMU) , München, Deutschland

Purpose: Cervical cancer incidence is decreasing both globally and in

Germany. e objective of this study was to analyse prognostic factors

and outcomes of invasive cervical cancer in a population-based setting.

Methods: 2,291 cervical cancer patients diagnosed between 2007 and

2016 within the catchment area of the Munich Cancer Registry (MCR)

were analysed regarding prognostic factors and outcomes. Cumulative in-

cidence was used to calculate time to locoregional recurrence and distant

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metastases. Survival was assessed using the Kaplan–Meier method, rela-

tive survival (RS) analysis, and a Cox proportional hazards model.

Results: e majority (48.7%) of the comparatively young (median age:

52 years) cervical cancer patients was diagnosed at an early tumor stage

(IA1,IA2,IB1), while 14.3% presented with metastatic disease at the time

of diagnosis. e proportion of patients with positive lymph nodes in-

creased with stage, with no lymph node involvement in stage IA1, and

up to 42.8% in stage IIB. e analysis of time to locoregional recurrence

and metastasis showed a respective 5-year cumulative incidence rate of

10.1% and 13.4%. ere was only a slight improvement in overall (5-year:

68.1%) and relative (5-year: 71.5%) survival rates over time. Stratied by

stage the 5-year overall survival ranges from 98.9% in stage IA1, to 61,6%

in IIB, and 16,6 % in patients with metastases (M1). A cox model revealed,

as expected, a statistically signicant association of age (p<0.001), stage

(p<0.001), grade (p<0.01), lymph vessel invasion (p<0.01), and histology

(p<0.01) with survival.

Conclusions: e prognosis in cervical cancer is comparatively good,

caused by the high percentage of patients diagnosed at an early stage. Un-

fortunately there is only a slight improvement in prognosis over time.

493

Trends in Prognostic Factors and Outcomes of Ovarian Cancer

Patients Over a 20-Year Period (1997-2016)

MiriamRottmann 1; Alexander Burges 2; Sven Mahner 2;

Christine E. Brambs 3; Marion Kiechle 3; Martin Pölcher 4; Dieter Grab 5;

Christoph Anthuber 6; Andreas Schnelzer 7; Franz Edler von Koch 8;

Doris Mayr 9; Wilko Weichert 10; Gabriele Schubert-Fritschle 1; Jutta Engel 1

1Tumorregister München (TRM), Bayerisches Krebsregister - Regionalzentrum

München (LGL), am Klinikum der Universität München, Institut für Medizinische

Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Ludwig-

Maximilians-Universität (LMU), München, Deutschland

2Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der

Universität München, München, Deutschland

3Frauenklinik rechts der Isar, Universitätsklinikum Rechts der Isar der

Technischen Universität München (TUM), München, Deutschland

4Rotkreuzklinikum München Frauenklinik, München, Deutschland

5Klinik für Frauenheilkunde, Geburtshilfe und Chirurgie, München Klinik

Harlaching, München, Deutschland

6Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Starnberg, Starnberg,

Deutschland

7Klinik für Gynäkologie und Geburtshilfe, RoMed Klinikum Rosenheim,

Rosenheim, Deutschland

8Klinik für Gynäkologie und Geburtshilfe, Klinikum Dritter Orden, München,

Deutschland

9Pathologisches Institut, Medizinische Fakultät, LMU München, München,

Deutschland

10Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische

Universität München, München, Deutschland

Purpose: Signicant eort has been made to improve the poor prognosis

of invasive ovarian cancer patients. e objective of this study was to anal-

yse prognostic factors and invasive ovarian cancer patient outcome over

time in a population-based setting.

Methods: 6,984 ovarian cancer patients diagnosed between 1997 and

2016 within the catchment area of the Munich Cancer Registry (MCR)

were analysed. Patients diagnosed 1997-2006 and 2007-2016 were com-

pared. Cumulative incidence (CI) was used to calculate time to progres-

sion. Survival was analysed using the Kaplan–Meier method (Overall sur-

vival, OS), calculation of relative survival (RS), and a Cox proportional

hazards model (OS).

Results: e incidence rate of invasive ovarian carcinoma decreased

over time from 23.8 (1997) to 16.5(2016) /100,000. e majority of the

patients continued to be diagnosed at an advanced stage of FIGO III or

IV. Furthermore, there was a slight increase (p=0.04) in the proportion

of patients diagnosed with FIGO III (45.4 vs 47.9%) and FIGO IV (23.1

vs 24.1%). While the proportion of patients that underwent surgery did

not change signicantly over time (87.0 vs 88.0%, p=0.25), an increase in

patients without residual disease was observed (50.2 vs 58.5%, p<0.001).

In patients with surgery, there was a slight improvement in time to

progression (5-year CI: 43.2 vs 41.0%, p=0.11), as well as in overall (5-

year OS: 41.2 vs 44.8%, p=0.04)) and relative (5-year RS: 44.6 vs 48.4%)

survival rates. e cox model revealed a signicant association of survival

with age (≥80 vs <50 HR 3.78, p<0.001), stage (FIGO IV vs I HR 5.54

p<0.001), residual disease (>1cm vs no residuals HR 2.09, p<0.001), and

chemotherapy (no chemo vs chemo HR 1.44, p<0.001).

Conclusions: Ovarian cancer remains a very challenging disease that

needs to be treated with highest standards. Patients undergoing successful

treatment, especially with regard to surgery, showed an improvement in

survival over time. is may primarily be due to the signicant increase

in the proportion of patients that underwent surgery without residual

disease.

497

Combined Assessment of 3Q26 Amplication and Promoter

Methylation in Patients with High Grade Cervical Lesions

Show Age Specic Dierences

Josene Beiersdorf 1; Cornelia Scheungraber 1; Kristina Wunsch 2;

Martina Schmitz 2; Alfred Hansel 2; Heike Hoyer 3; Mieczyslaw Gajda 4;

Christiane Greinke 1; Ingo B. Runnebaum 1; Claudia Backsch 1;

Matthias Dürst 1

1Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,

Universitätsklinikum Jena, Friedrich Schiller Universität, Jena, Deutschland

2oncgnostics GmbH, Jena, Deutschland

3Institut für Medizinische Statistik, Informatik und Datenwissenschaften,

Universitätsklinikum Jena, Friedrich Schiller Universität

4Institut für Rechtsmedizin, Sektion Pathologie, Universitätsklinikum Jena,

Friedrich Schiller Universität, Jena

Purpose: A considerable proportion of high grade cervical intraepitheli-

al lesions (CIN2/3) are known to resolve on their own especially among

young women. However, since reliable prognostic markers are still lack-

ing, the diagnosis “CIN3” is still an indication for surgery which may

result in overtreatment. It is conceivable that a combination of dierent,

ideally independent molecular markers may provide more reliable results.

In the present cross-sectional study two established triage markers, 3q26

amplication and a methylation signature, were evaluated in an age-de-

pendent manner.

Methods: e patient cohort comprised 60 patients with histologically

conrmed CIN2/3 in two equally sized age groups (<30 years, ≥30 years).

Cervical scrapes were analyzed by interphase uorescence in situ hybrid-

ization for 3q26 amplication and methylation specic PCR (GynTect®)

for six dierent genome regions.

Results: Both assays showed a signicantly dierent pattern of test out-

come independent of age (P=0.001). Moreover, the combination of both

assays diered signicantly for double positive and double negative cas-

es when comparing the two age groups: In patients <30 years there were

clearly less cases with positive methylation signature and amplication

of 3q26 as in women ≥30 years (23% versus 63%, Bonferroni adjusted

P=0.016). Of particular interest is the nding that double negative results

were exclusive for the young age group (0% versus 27%, Bonferroni ad-

justed P=0.020).

Conclusions: Since regression of CIN2/3 characteristically occurs among

young women it is tempting to speculate that a double negative test result

could be prognostic for regression of CIN2/3. is will have to be investi-

gated further in a prospective longitudinal intervention study.

Disclosure Statement: no conicts of interest to disclose

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559

A Real-World Experience of Multiple Lines of Bevacizumab-

BASED Therapy in Patients with Pretreated Recurrent

Tuboovarian Carcinoma

Christian M. Kurbacher 1; Valérie Kallage 2; A. Tabea Kurbacher 1;

Susanne Herz 1; Alexander Schott 1; Gabriele Kolberg 1; Claudia

Schweitzer 1; Jutta Anna Kurbacher 3

1Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie I (Schwerpunkt:

Gynäkologische Onkologie), Bonn

2Frauenklinik, St. Katharinen-Hospital, Frechen

3Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine

Gynäkologie und Geburtshilfe), Bonn

Purpose: is retrospective study sought to yield more concise data on

multiple lines of Bevacizumab (Bev)-based therapy (Tx) in patients (pts)

with recurrent tuboovarian carcinoma (TOC).

Methods: 90 pts with recurrent TOC were included. 37 (41.1%) pts had

one, 20 (22.2%) had two, 13 (14.4%) had three and 20 had (22.2%) 4-9

lines of Bev. A total of 225 courses of Bev-based treatment were adminis-

tered: 58 (25.8%) as monotherapy (Bev), 63 (28.0%) in combination with

conventionally dosed Ctx (Bev+cCtx), and 104 (46.2%) in combination

with metronomic Ctx (Bev+mCtx). Time to progression (TTP) was calcu-

lated from the start of each Bev-based Tx until progression, overall surviv-

al was calculated from the start of the rst Bev-based Tx until death from

any reason or loss to follow-up. Adverse eects in regard to Bev Tx were

scored according to CTCAE vs 4.02.

Results: Bev-related G3-4 toxicities comprised hypertension in 2.2%,

bowel obstruction in 0.9%, small bowel perforation in 0.9%, nephrotic

syndrome in 0.4% and infection seen in 1.3% of treatments. Both TTP

and OS were not signicantly dierent between dierent types of Tx. TTP:

Bev, 5.4 months (ms); Bv+cCtx, 6.1 ms; Bev+mCtx, 6.3 ms. OS: Bev, 28.6

ms, Bev+cCtx, 31 ms; B+mCtx, 21.4 ms. TTP was comparable between

one and multiple lines of Bev: one line, 6.6 ms; two lines, 6.3 ms, three

lines 5.9 ms, and >4 lines 3.7 ms (p=0.130). However, OS increased sig-

nicantly with the number of Bev-based lines of Tx: one line, 8.8 ms; two

lines, 16.8 ms; three lines 25.4 ms; >4 lines, 36.6 ms (p=0.0001).

Conclusions: Retreatment with Bev is safe and eective in a real-world

population of pts with recurrent TOC. e number of Bev-based lines had

a signicant impact on overall survival.

Disclosure Statement: All authors declare no conicts of interest

637

Tissue Factor Expression of Extracellular Vesicles from

Ascites of Ovarian Cancer Patients Correlates with Venous

Thrombembolic Events (VTE)

Fanny Ender 1; Corinna Steidel 1; Nikolas von Bubno 1; Achim Rody 2;

Frank Gieseler 1

1Clinic for Hematology and Oncology, UKSH Lübeck, Lübeck, Deutschland

2Department of Gynecology, UKSH Lübeck, Lübeck, Deutschland

Purpose: As malignant eusions (e.g. ascites) contain cells, cellular com-

ponents, growth factors, and cytokines, they mirror the microenviron-

ment of tumors. Oen, patients with ovarian carcinoma suer from both

deregulated immune mechanisms and systemic hyper coagulation. As a

molecular link, tissue factor-bearing small Extracellular Vesicles (EVs)

may play a decisive role in the systemic coagulation via activation of the

extrinsic tenase as well as in tumor cell activation via the PAR2/G-pro-

tein/ERK-pathway1.

Methods: Here, we obtained ascites from ovarian carcinoma patients from

the Clinic for Gynecology of the University Medical Center Schleswig-

Holstein collected during surgery or paracentesis. EV subgroups

(exosomes, ectosomes) were isolated and separated using sequential

centrifugation as described elsewhere2. Using annexin-V coated

magnetic beads, phosphatidylserine+ EVs were specically enriched3.

EV subpopulations were then characterized using high-resolution ow

cytometry as well as electron microscopy and analyzed regarding their

procoagulant properties (PS, TF activity). Results were correlated with

clinically overt VTEs.

Results: Ascites from patients with ovarian cancer contained high

amounts of EVs that exposed varying amounts of PS and TF on their

surface. Interestingly, PS and TF were co-expressed. Isolation using an-

nexin-V coated magnetic beads resulted in a signicant enrichment of

TF+EVs. Notably, TF expression on EVs signicantly correlated with clin-

ically reported VTEs4.

Conclusions: is small study indicates the clinical value of EV diagnos-

tic in human body liquids. However, standardized methods for the isola-

tion of EV subpopulations (exosomes, ectosomes), as well as for quanti-

cation and characterization have to be used in order to get reliable and

comparable results.

References:

1. Ender et al., Anticancer Res 2019

2. Gieseler et al., Cell Biol Int 2018

3. Gieseler et al., Cell Biol Int 2014

4. Gieseler and Ender, Proceedings on Cancer-Immuno-Oncology 2018

Disclosure Statement: e Authors declare no conict of interest.

669

Analysis of Methylation Marker for Circulating Tumor DNA

of Epithelial Ovarian Cancer (EOC) – The Assurer Project

Norman Haefner; Sabrina Noack; Miriam Stein; Herbert Diebolder;

Matthias Dürst; Ingo B. Runnebaum

Universitätsklinikum Jena, Klinik für Frauenheilkunde und

Fortpanzungsmedizin, Jena, Deutschland

Purpose: e lack of early detection assays and the occurrence of un-

specic symptoms are causative for the late diagnosis of EOC. Aberrant

DNA methylation of cell-free DNA (cfDNA) may be a potential biomark-

er for EOC.

Methods: Genome wide methylation analyses of tissue-derived gDNA

and cfDNA from blood were used to identify candidate regions. Marker

validation was realized with two sample sets by methylation specic PCR

(MSP) using bisulte-treated cfDNA (set 1: benigne controls n=67 and

EOC n=68 (FIGO III/IV); set 2: EOC n=43 (FIGO I-IV) and age matched

healthy women n=14).

Results: Analyses of tissues (EOC n=33, normal ovaries n=3, white blood

cells n=4) lead to the identication of potential candidates for cfDNA

analysis. e comparison with published data resulted in the selection

of 50 candidate regions for validation. ree top candidates reached a

sensitivity and specicity of 27-57% and 91-100%, respectively. e best

two-marker combination exhibited 63.2% sensitivity and 95.5% specic-

ity. For one of these three markers a low methylation level in the tumor

tissue can explain the absence of methylation in cfDNA. Intratumoral

heterogeneity and the methylation state in early stage disease point to hy-

permethylation of one candidate as potentially late event in EOC develop-

ment. To identify additional markers the genome wide analysis of cfDNA

was established and is presently conducted.

Conclusions: e specic and sensitive detection of EOC-specic aber-

rant DNA methylation in cfDNA is possible. e direct analysis of cfD-

NA for marker identication should result in an improved diagnostic

performance to enable the early detection with DNA-methylation-based

biomarkers.

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684

Safety and Eectiveness of Bevacizumab (BEV)-ContainIng

Therapy in Patients (PTS) with Primary Ovarian Cancer (OC):

Interim Analyses of The Otilia German Non-Interventional

Study

Jalid Sehouli 1; Alexander Mustea 2; Guelten Oskay-Özcelik 3; Maren Keller 4;

Rolf Richter 1; Oliver Tomé 5; Hannah Woopen 1; Ann-Kathrin Sommer 6;

Jacek Grabowski 1; Robert Armbrust 1; Pauline Wimberger 7

1Charité Campus Virchow Klinikum, Department of Gynecology with Center for

Oncological Surgery, Berlin, Deutschland

2University Hospital Bonn, Bonn, Deutschland

3Praxisklinik Krebsheilkunde für Frauen, Berlin, Deutschland

4North-Eastern-German Society of Gynaecological Oncology (NOGGO e.V.), c/o

Charité Medical University of Berlin, Berlin, Deutschland

5St. Vincentius-Kliniken, Department of Gynecology, Karlsruhe, Deutschland

6Roche Pharma AG, Grenzach-Wyhlen, Deutschland

7Carl-Gustav-Carus University Dresden, TU Dresden, Gynecology and Obstetrics,

Dresden, Deutschland

Purpose: BEV combined with carboplatin plus paclitaxel (CP) is approved

as front-line therapy for FIGO (1998) stage IIIB–IV OC. e ongoing sin-

gle-arm non-interventional OTILIA study (NCT01697488) was initiated

to assess the safety and eectiveness of front-line BEV-containing therapy

in the real-world setting in Germany. Here we present results of the 2nd

and 3rd interim analysis.

Methods: Pts with FIGO stage IIIB–IV OC received front-line BEV +

CP. Adverse events were recorded at each cycle and graded using CTCAE

v4.0. Investigators assessed response according to local practice. Patients

were followed for 12 months aer disease progression, discontinuation of

BEV or completion of 15 months of BEV therapy. Exploratory analyses

compared safety and ecacy according to age, Eastern Cooperative On-

cology Group performance status (ECOG PS), and comorbidities.

Results: 808 pts were analyzed, of whom 704 had completed documenta-

tion. Estimated median BEV treatment duration was 13.4 months (95%

CI 12.8–13.8). 433 (62%) had discontinued therapy prematurely. Median

progression-free survival (PFS) was 21.3 months (95% CI 20.3–22.5) in

the overall population. ere was no apparent dierence in PFS according

to age, ECOG PS, or between comorbidity subgroups and the overall pop-

ulation. Comorbidities were more common in pts aged ≥70 (47%) than

<70 years (53%). Tolerability was similar in subgroups aged ≥70 versus

<70 years (all grades, 74% vs. 70%; grade 3/4, 35% vs. 32%; serious AE,

31% vs. 24%).

Conclusions: e interim analyses of this large observational trial in-

dicate the favorable eectiveness and tolerability of BEV- maintenance

therapy for pts with newly diagnosed OC treated in a real-world setting.

Exploratory analyses of OTILIA showed no association of age with worse

outcome with respect to (preliminary) ecacy or tolerability. PFS results

of patients with comorbidities were in line with those of the overall pop-

ulation, despite older age and worse ECOG PS. is study underlines that

BEV is a safe and eective treatment option independently of age and co-

morbidities.

Conicts of Interest: J. Sehouli: Honoraria: AstraZeneca, Clovis Oncol, Eisai,

Johnson & Johnson, MSD Oncology, Olympus Medical Systems, Pzer, Phar-

maMar, Tesaro, Teva; Consulting or Advisory Role: AstraZeneca, Clovis Oncology,

Lilly, Merck, MSD Oncology, Pzer, PharmaMar, Tesaro; Research Funding: Astra-

Zeneca (Inst), Bayer (Inst), Clovis Oncology (Inst), Merck (Inst), MSD Oncology

(Inst), Pzer (Inst), PharmaMar (Inst), Tesaro (Inst); Travel, Accommodations,

Expenses: AstraZeneca, Clovis Oncology, MSD Oncology, PharmaMar, Roche

Pharma AG, Tesaro.

A. Mustea: Consulting or Advisory Role: AstraZeneca. Roche

G. Oskay-Özcelik: Honoraria: Roche, Novartis, AstraZeneca, AMGEN, Riemser;

MSD; Consulting or Advisory Role: Roche, Novartis, AstraZeneca, MSD

M. Keller: No Relationships to Disclose

R. Richter: No Relationships to Disclose

O. Tomé: No Relationships to Disclose

H. Woopen: Travel, Accommodations, Expenses: Medac

A.-K. Sommer: Employee of Roche

J.P. Grabowski: Honoraria: AstraZeneca, Clovis Oncology, Pzer, RIEMSER,

Roche, Tesaro. Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Pzer,

RIEMSER, Roche, Tesaro; Research Funding: AstraZeneca (Inst), MSD (Inst),

RIEMSER (Inst), Tesaro (Inst); Travel, Accommodations, Expenses: Molecular

Health, Tesaro.

R. Armbrust: No Relationships to Disclose

P. Wimberger: Honoraria: Roche; AstraZeneca; Clovis Oncol; Eisai; Novartis;

Amgen; MSD; Merck; Oncology; Pzer; PharmaMar; Tesaro; Teva; Research

Funding: Amgen; Novartis; RocheConsulting or Advisory Role: Roche; MSD;

Tesaro; Novartis; Amgen; Clovis; Pzer; AstraZeneca; Eisai

691

Phase III PAOLA-1/ENGOT-OV25 Trial: Olaparib Plus

Bevacizumab (BEV) As Maintenance Therapy in Patients (PTS)

with Newly Diagnosed, Advanced Ovarian Cancer (OC) Treated

with Platinum-Based Chemotherapy (PCH) Plus Bev

Nikolaus de Gregorio 1; Philipp Harter 2; Jalid Sehouli 3; Ulrich Canzler 4;

Frederik Marme 5; Paul Buderath 6; Hans-Joachim Lück 7;

Martina Gropp-Meier 8; Ingo B. Runnebaum 9; Antje Belau 10;

Stefan Renner 11; Barbara Schmalfeldt 12; Ahmed El-Balat 13;

Alexander Burges 14; Peter Hillemanns 15; Dominik Denschlag 16;

Dirk Bauerschlag 17; Lars Hanker 18; Andreas Schnelzer 19;

Isabelle Ray-Coquard 20

1Ulm, Universitätsfrauenklinik Ulm, Ulm, Deutschland

2Klinikum Essen Mitte

3Charite Berlin

4Universitätsfrauenklinik Technische Universität Dresden, Dresden, Deutschland

5Universitätsfrauenklinik Heidelberg

6Universitätsfrauenklinik Essen

7Gynäkologisch Onkologische Praxis Hannover

8KH St. Elisabeth Ravensburg

9Universitätsfrauenklinik Jena

10Universitätsfrauenklinik Greifswald

11Universitätsfrauenklinik Erlangen

12Universitätsfrauenklinik Hamburg Eppendorf

13Universitätsfrauenklinik Frankfurt

14Universitätsfrauenklinik München Großhadern

15Medizinische Hochschule Hannover

16Hochtaunuskliniken Bad Homburg

17Universitätsfrauenklinik Kiel

18Universitätsfrauenklinik Lübeck

19Universitätsfrauenklinik rechts der Isar TU München

20Centre Léon BERARD, Lyon, Lyon, Frankreich

PAOLA-1 Study

Purpose: PAOLA-1/ENGOT-ov25 (NCT02477644) is the rst Phase

III trial to evaluate the ecacy and safety of a PARP inhibitor with bev

as rst-line (1L) maintenance therapy for advanced OC, regardless of

BRCA1/2 mutation (BRCAm) status. Please copy and paste the

Methods: PAOLA-1 is a randomized, double-blind, international Phase

III trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade

serous or endometrioid OC, fallopian tube or primary peritoneal cancer.

Pts had received standard PCh plus bev and were in clinical complete or

partial response. Pts were randomized (2:1) to Olaparib tablets (300 mg

bid for up to 24 months [m]) plus bev (15 mg/kg, d1, q3w, for 15 m in-

cluding when combined with PCh) or placebo (pbo) plus bev, stratied by

1L treatment outcome and tumour BRCAm status. e primary endpoint

was investigator-assessed progression-free survival in the intent-to-treat

population (PFS; modied RECIST v1.1).

Results: e primary endpoint in the intent-to-treat population showed a

statistically signicant and clinically meaningful improvement in progres-

sion-free survival (PFS). e safety and tolerability proles observed in

PAOLA-1 were generally consistent with those known for each medicine.

Conclusions: In patients with advanced primary ovarian cancer, main-

tenance Olaparib resulted in a statistically signicant PFS improvement.

is is the rst time this was demonstrated regardless of BRCA mutation

status.

Literature: not applicable

Disclosures: will be shown in the nal presentation with updated information on

disclosures of all 20 authors

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778

Laparoscopic Radical Hysterectomy in Cervical Cancer:

Is Peritoneal Contamination with Tumor Cells an

Underestimated Event?

Rüdiger Klapdor; Hermann Hertel; Peter Hillemanns;

Matthias Jentschke

Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule

Hannover, Hannover, Deutschland

Purpose: Peritoneal dissemination of cervical cancer cells during intra-

corporal colpotomy might be responsible for reduced disease free surviv-

al aer laparoscopic radical hysterectomy as shown in the LACC study.

However, data on the frequency or mechanisms of peritoneal contamina-

tion are missing. erefore, we aimed to analyze peritoneal contamination

of cervical secretion during intracorporal colpotomy with a novel indocy-

aningreen (ICG) -based technique.

Methods: In this prospective study, we evaluated patients undergoing

routine laparoscopic or robot-assisted hysterectomy for benign indica-

tions. Routine surgery was performed aer application of ICG specically

to the cervical surface. During and aer colpotomy pictures under white

and uorescence light were taken in order to evaluate frequency and ex-

tent of peritoneal contamination.

Results: Peritoneal contamination during intracorporal colpotomy oc-

curred in 9/12 (75%) patients undergoing routine laparoscopic hysterec-

tomy. Laparoscopic instruments were contaminated in 60% of all cases.

Extent of contamination varied between individual patients with a medi-

an grade of 2.75 (range 1-4.5; 1 no contamination - 5 strong contamina-

tion) at posterior colpotomy. ere were no adverse eects during surgery.

Conclusions: Peritoneal contamination with cervical secretion is a fre-

quent event during intracorporal colpotomy. We describe a promising

tool for feasible and direct visualization of peritoneal contamination

during laparoscopic colpotomy. is may be easily implemented in fur-

ther studies on laparoscopic radical hysterectomy and serve as a quality

assessment tool for surgeons and surgical techniques.

Disclosure Statement: All authors declare no conict of interest.

815

Sentinel Lymph Node Dissection in Vulvar Cancer. A Survey

About Knowledge, Status and Counseling in Outpatient

Sector

Marlene Röttger; Hermann Hertel; Peter Hillemanns; Rüdiger Klapdor

Frauenklinik, Medizinische Hochschule Hannover, Hannover, Deutschland

Purpose: Sentinel lymph node dissection is an alternative to radical

lymph node dissection (LND) for early vulvar cancer. Patient selection

and counseling is key for a safe use of SLND (1). Our aim was to evaluate

how gynecologists in an outpatient setting think about SLND, counsel pa-

tients and select hospitals for further treatment.

Methods: A questionnaire containing 29 questions about SLND in vulvar

cancer was sent to gynecologists in Lower Saxony via mail and letter. e

questionnaire contained multiple choice questions and open questions.

e study was approved by the local ethics committee.

Results: e median age of the 80 respondents was 54.5 (26-66) years.

Most (86%) participants reported to only treat one to ve patients with

vulvar cancer per year. Interestingly, 70% and 64% of the gynecologists

send their patients to university hospitals or hospitals oering maximum

care, respectively. Of all, 33% replied that SLND was performed rarely or

never in their patients. e gynecologists answered that only 40% of the

patients are well informed about advantages and possible disadvantages

of SLND. Most (95%) felt responsible to counsel patients on treatment

decisions independently from or additionally to the hospital. Of all, 78%

replied that they are not completely sure about the exact recurrence rates

aer SLND. Of notice, 68% believe that SLND for vulvar cancer is safe if

applied in specialized centers and 92% stated that focusing patients on

specialized centers is required for best results.

Conclusions: Gynecologists in the outpatient setting play a crucial role

for counseling and admission of patients to the hospitals. A close com-

munication between hospital and outpatient gynecologists appears to be

essential to select optimal treatment strategies for individual patients.

Reference:

1. Diagnosis, erapy, and Follow-Up Care of Vulvar Cancer and its Precursors.

National Guideline of the German Society of Gynecology and Obstetrics

(S2k-Level, AWMF Registry No. 015/059, August 2015).

Disclosure Statement: All authors have no conicts of interest.

837

Characterization of Tribbles 1 in Epithelial Ovarian Cancer

Leonard Bauerschmitz; Vanessa Raddatz; Matthias Dürst;

Ingo B. Runnebaum; Norman Haefner

Universitätsklinikum Jena, Klinik für Frauenheilkunde und

Fortpanzungsmedizin, Jena, Deutschland

Purpose: We have identied TRIB2 a member of the Tribbles protein

family as mediator of cisplatin sensitivity in epithelial ovarian cancer

(EOC; Ref.1). e aim of the presented project is the characterization of

Tribbles 1 (TRIB1).

Methods: Gene expression analyses of clinical samples (EOC type II,

FIGO III/IV, n=38) and cell lines were done by qRT-PCR. In-vitro analy-

ses were conducted aer stable overexpression of TRIB1 using retroviral

transduction of A2780 (parental and resistant cultures) and OVCAR3

cells. Functional readouts consist of IC50 determination against cisplatin,

proliferation and colony formation assays.

Results: TRIB1 RNA expression was signicantly higher in parental cell

lines or platin sensitive EOC patients compared to resistant sub-cultures

and patients, respectively. Moreover, parental sensitive cell lines revealed a

time and concentration dependent upregulation of TRIB1 under cisplatin

treatment, whereas resistant cells exhibited a more stable TRIB1 expres-

sion. EOC patients stratied by the median TRIB1 expression resulted

in groups with signicantly dierent PFS and OS. Patients with TRIB1-

high tumors had a longer survival than patients with TRIB1-low tumors

(p<0.05, LogRank test). e successful overexpression of TRIB1 in paren-

tal and resistant A2780 cells (>10-fold increase of transcript level) did not

result in changed IC50 values for cisplatin.

Conclusions: Although TRIB1 gene expression is potentially prognos-

tic for EOC and is aected by cisplatin exposure similarly to the TRIB2

expression, its overexpression cannot reverse the resistant phenotype

in A2780. Presently, both the validation in other EOC cell lines and the

exploration of the molecular dierences between TRIB1 and TRIB2 are

conducted.

Reference:

1. Kritsch et al. Tribbles 2 mediates cisplatin sensitivity and DNA damage respon-

se in epithelial ovarian cancer. Int J Cancer. 2017 Oct 15;141(8):1600-1614

843

Adapted Adjuvant TC Chemotherapy in Primary Tubal Cancer

After Renal Transplantation and Chronic Hepatitis

C Infection - A Case Report

Peter Ugocsai; Madeleine Hetterich; Paolo Gennari; Attila Teoman;

Atanas Ignatov; Olaf Ortmann; Stephan Seitz

Department of Gynecology and Obstetrics, University Medical Center

Regensburg, Regensburg, Deutschland

Purpose: Application of a platinum-based chemotherapy in patients with

impaired renal function or taxanes in case of liver disorders is challeng-

ing. Strategies suggested applying platinum at a GFR <15ml/min include a

dose reduction with subsequent dialysis (DIA). Considering taxanes, due

to a possible hepatitis C reactivation a close monitoring with temporary

discontinuation and subsequent dose reduction is suggested.

Methods: Presentation 74-year old patient with renal impairment follow-

ing a renal transplantation and a chronic hepatitis C infection with the

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2018

clinical picture of an ovarian cancer. Following an exploratory laparot-

omy, a primary high-grade serous fallopian tube cancer was conrmed,

FIGOIIIb, with the operative achievement of a macroscopic disease-free

status (R0). e adjuvant chemotherapy with paclitaxel (TAX) and car-

boplatin (CAR) was adapted to the impaired renal function and hepatic

status: TAX 140mg/m2, followed aer 48 hours by CAR 125mg/m2 with

a subsequent DIA aer 20 hours (AUC 3-5 mg·min/ml) (d1[TAX], d3[-

CAR], d4[DIA] / q3w).

Results: Hematotoxicity with anemia and thrombocytopenia, without

signs of leukopenia appeared aer 3 cycles resulting in a further dose

reduction of TAX. Anemia was treated with regular blood transfusions

during DIA. e treatment was discontinued aer 5 cycles due to a se-

vere thrombocytopenia. Relapse occurred aer 10 months. 2nd line treat-

ment was initiated with liposomal doxorubicin in monotherapy (d1/q4w),

which was discontinued aer 3 cycles due to a severe thrombocytopenia

and disease progression, followed by best supportive care.

Conclusions: : In case of a combined renal and hepatic impairment we

suggest during a combined TC treatment TAX in reduced dose and the

time-delayed application of CAR along with a hemato-nephroprotec-

tive dialysis within 24 hours. According to the observed hematological

toxicity of TC, apart from transfusion of red blood cells, the continuous

application of thrombopoietin during the cytotoxic treatment should be

considered.

Disclosure Statement: no conict of interest

Head and Neck Cancer

Poster

194

Nivolumab Adjuvant in Combination with Postoperative

Radiotherapy and as Maintenance in Patients with

Intermediate Risk Locally Advanced Head and Neck

Cancer – The NadiHN Trial

Franz-Georg Bauernfeind 1; Henning Schäfer 2; Matthias Hautmann 3;

Thomas Gauler 4; Rolf Mahlberg 5; Wilfried Budach 6; Balint Tamaskovics 6;

Rene Baumann 7; Michael Eble 8; Justin Hasenkamp 9; Adriane Koppelle 10;

Anke Reinacher-Schick 10; Ste Pigorsch 11; Anne Lammert 12; Lisa Meert 1;

Anca-Ligia Grosu 2; Dariusch Hadizadeh 13; Glen Kristiansen 14;

Martina Heimann 15; Andreas Dietz 16; Peter Brossart 1

1Medizinische Klinik III, Universitätsklinikum Bonn, Bonn, Deutschland

2Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg,

Deutschland

3Klinik für Strahlentherapie, Universitätsklinikum Regensburg, Regensburg,

Deutschland

4Klinik für Strahlentherapie, Universitätsklinikum Essen, Essen, Deutschland

5Medizinische Klinik I, Mutterhaus Trier, Trier

6Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum

Düsseldorf, Düsseldorf

7Klinik für Radio-Onkologie, Marien-Krankenhaus Siegen, Siegen

8Klinik für Strahlentherapie, Universitätsklinikum Aachen, Aachen

9Abteilung für Hämatologie und Onkologie, Universitätsmedizin Göttingen,

Göttingen

10Abteilung für Onkologie, Universitätsklinikum Bochum, Bochum

11Klinik für Radioonkologie und Strahlentherapie, Technische Universität

München, München

12HNO-Klinik, Universitätsmedizin Mannheim, Mannheim

13Abteilung für Radiologie, Universitätsklinikum Bonn, Bonn

14Institut für Pathologie, Universitätsklinikum Bonn, Bonn

15Abteilung für Strahlentherapie, Universitätsklinikum Bonn, Bonn

16HNO-Klinik, Universitätsklinikum Leipzig, Leipzig

Purpose: Adjuvant radiotherapy is the standard of care in postoperative

patients with locally advanced head and neck squamous cell carcinoma

(HNSCC) and adequate R0 resection in the absence of extracapsular

lymph node extension (ece). Immunotherapy with the check point in-

hibitor Nivolumab has signicantly improved the outcome of relapsed/

refractory HNSCC patients. Preclinical data suggest that the combination

of photon radiation with PD-1 targeting immunotherapies may strength-

en immune responses. is two-armed, randomized, open-label phase

II trial evaluates the ecacy of combined adjuvant immunotherapy and

radiation therapy.

Methods: 176 patients with locally advanced stage HNSCC (R0, ece-) will

be included. 88 patients will be randomized to receive standard of care

adjuvant 60 Gy IMRT (standard arm). 88 patients will additionally receive

Nivolumab (experimental arm). Nivolumab will be given once prior to

radiotherapy (RT), concurrently to RT and over 3 months every 2 weeks

aer RT. en, Nivolumab will be additionally applied as maintenance

therapy over the course of additional 9 months every 4 weeks. erapy

will be stopped in case of progression or unacceptable toxicity.

Results: e primary endpoint will be disease free survival. Secondary

endpoints will be overall survival, safety and quality of life. An extensive

exploratory translational research program attached to this trial will focus

on mechanisms of the immune-stimulating eect of radiotherapy and the

identication of potential biomarkers predicting response to Nivolumab.

40 patients have been recruited by July 2019. e detailed treatment pro-

tocol and accrual data will be presented.

Conclusions: e NadiHN trial will contribute prospective data to the

level of ecacy of adjuvant immunotherapy with Nivolumab and safety

data on the combination of photon radiation and immunotherapy with

Nivolumab in the postoperative setting where single adjuvant radiation

therapy would be the standard of care.

Disclosure Statement: EudraCT 2016-004787-20; Funding: Bristol-Myers Squibb

GmbH & Co. KGaA.

200

Oncogenic BTK Promotes Growth and Vascularization

of Head and Neck Squamous Cell Carcinoma (HNSCC) in Vitro

and in Vivo

Anna-Rebekka Staufenberg 1; Hannah Strobel 1; Kristina Lesakova 1;

Ninel Azoitei 2; Johanna Sporleder 1; Jasmin Ezić 1; Julia Kolarova 3;

Robert Drees 1; Stephanie E. Weissinger 4; Alexey Ushmorov 5;

Johannes Döscher 1; Marie-Nicole Theodoraki 1; Patrick Schuler 1;

Simon Laban 1; Ole Ammerpohl 3; Thomas K. Homann 1;

Emanuela Grassili 6; Cornelia Brunner 1

1Ulm University Medical Center, Department of Oto-Rhino-Laryngology, Ulm,

Deutschland

2Ulm University Medical Center, Department of Internal Medicine I, Ulm,

Deutschland

3Ulm University Medical Center, Institute of Human Genetics, Ulm, Deutschland

4Ulm University Medical Center, Institute of Pathology, Ulm, Deutschland

5Ulm University, Department of Physiological Chemistry, Ulm, Deutschland

6University of Milano-Bicocca, School of Medicine and Surgery, Monza, Italien

Purpose: Recently, two novel BTK (Bruton’s Tyrosine Kinase) isoforms

of 80 and 65 kDa have been described to be expressed in solid carcino-

ma entities and therein BTK expression seemed to be linked with tumor

growth and protection from apoptosis resulting in a poor prognosis of

these cancer patients. Until these observations, no BTK expression out-

side the hematopoietic system has been reported. erefore, we aimed to

investigate whether BTK isoforms are also expressed in HNSCC and to

further elucidate the molecular and cellular consequences of BTK expres-

sion for HNSCC tumorigenesis.

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Methods: HNSCC-derived cell lines as well as tumor samples were ana-

lyzed for BTK-p65 and –p80 expression. e consequences of pharmaco-

logical and genetic inhibition of BTK activity for proliferation, cell cycle

progression, transmigration, apoptosis and vascularization were analyzed

in vitro and in vivo. BTK-promoter methylation studies were performed.

Results: BTK-p65 and -p80 isoforms are expressed in HNSCC cell lines as

well as in primary HNSCC samples. Pharmacological or genetic targeting

of BTK activity leads to inhibition of cell proliferation, transmigration as

well as VEGF secretion in vitro. ese eects were associated with cell

cycle arrest and induction of apoptosis. Moreover, in in vivo xenogra ex-

periments, chemically abrogation of BTK activity impaired tumor growth

and was associated with decreased tumor vascularization. BTK-promoter

methylation studies revealed a regulation of oncogenic Btk expression by

epigenetic alterations.

Conclusions: Together, our data characterize BTK-p65 as well as BTK-p80

as novel HNSCC-associated oncogenes representing crucial players in the

maintenance of HNSCC. us, targeting BTK-activity appears to be a

promising therapeutic option for patients suering from BTK-expressing

HNSCC.

Disclosure Statement: Nothing to disclose

259

Hanna - Real-World Data from a Non-Interventional Study

Assessing Routine Use of Nivolumab in Patients with

Recurrent or Metastatic Cancer of the Head and Neck

(R/M SCCHN) in Germany

Manfred Welslau 1; Eyck von der Heyde 2; Thomas Gauler 3; Dennis Hahn 4;

Ulrike Bockmühl 5; Claus Wittekindt 6; Harald Müller-Huesmann 7;

Chia-Jung Busch 8; Paul-Stefan Mauz 9; Daniela Waldenberger 10;

Andreas Dietz 11

1Klinikum Aschaenburg, Hämato-Onkologische Schwerpunktpraxis,

Aschaenburg, Deutschland

2Onkologische Praxis am Raschplatz, Hannover, Deutschland

3Universitätsklinikum Essen, Klinik für Strahlentherapie, Essen, Deutschland

4Klinikum der Landeshauptstadt Stuttgart, , Stuttgart, Deutschland

5Klinikum Kassel, Kassel, Deutschland

6Universitätsklinikum Gießen und Marburg, Gießen, Deutschland

7Brüderkrankenhaus St. Josef Paderborn, Paderborn, Deutschland

8Universitäts-Klinikum Hamburg-Eppendorf, Klinik und Poliklinik für Hals-,

Nasen- und Ohrenheilkunde, Hamburg, Deutschland

9Universitätsklinikum Tübingen, Klinik für Hals-, Nasen- und Ohrenheilkunde,

Tübingen, Deutschland

10Bristol-Myers-Squibb GmbH & Co. KGaA, München, Deutschland

11Universitätsklinikum Leipzig, Klinik und Poliklinik für Hals-, Nasen-,

Ohrenheilkunde, Leipzig, Leipzig, Deutschland

Purpose: Nivolumab (a fully human IgG4 monoclonal antibody target-

ing the PD-1 receptor on activated T-cells), is indicated in the EU for

the treatment of patients with R/M SCCHN progressing on or aer plat-

inum-based therapy. Results from CheckMate 141 (NCT02105636), the

pivotal trial evaluating nivolumab versus investigator’s choice (metho-

trexate, docetaxel, or cetuximab), demonstrated that patients treated with

nivolumab had signicantly improved overall survival (OS), higher re-

sponse rates, reduced adverse events, and maintained quality of life (QoL)

measures. e objective of this study is to assess real-world nivolumab

utilization, safety and outcomes in patients with R/M SCCHN.

Methods: HANNA is collecting real-world data on the routine treatment

of 385 patients with R/M SCCHN in 56 clinics and practices in Germa-

ny. Patients will be followed for 5 years from treatment initiation with

Nivolumab until death, withdrawal of consent, loss of follow-up/record

or to end of study. Primary objective is OS. Secondary objectives include

progression free survival, response rates, baseline characteristics, safety

proles and QoL.

Results: In this interim analysis, data of 300 patients with R/M SCCHN

regarding baseline-characteristics, eectiveness of the Nivolumab

treatment as well as safety and QoL under treatment will be presented.

e data provides information on disease and treatment characteristics,

prior treatment and ECOG performance status in an unselected patient

population.

Conclusions: Real-World data from HANNA reect use of Nivolumab in

routine clinical practice including patients with higher age and ECOG >2.

Recent results1 have shown that patients have a similar improvement in

outcomes, the treatment with Nivolumab was well tolerated and the QoL

stabilized under therapy.

Reference:

1. Dietz et al. DGHNO 2019, Oral presentation #101

Disclosure Statement: Amgen, Astellas, AstraZeneca, Bms, Celgene, Gilead,

Hexal, Janssen, Lilly, Medac, Novartis, Roche, Sano

287

Adenosine Receptor 2B Activity Promotes Autonomous

Growth, Migration As Well As Vascularization of Head

and Neck Squamous Cell Carcinoma Cells

Max Wilkat 1; Hanna Bast 1; Robert Drees 1; Johannes Dünser 1;

Magnus Brhel 1; Ninel Azoitei 2; Ralf Marienfeld 3; Felicia Frank 1;

Alexey Ushmorov 4; Jens Greve 1; Eva Goldberg-Bockhorn 1;

Marie-Nicole Theodoraki 1; Johannes Doescher 1; Simon Laban 1;

Patrick J. Schuler 1; Thomas K. Homann 1; Cornelia Brunner 1

1Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie ,

Universitätsklinik Ulm, Ulm , Deutschland

2Department of Internal Medicine I, Ulm University Medical Center

3Institute of Pathology, University of Ulm

4Department of Physiological Chemistry, University of Ulm

Purpose: Adenosine is a signaling molecule that exerts dual eects on

tumor growth: while it inhibits immune cell function, thereby prevent-

ing surveillance by the immune system, it also inuences tumorigenesis

directly via activation of adenosine receptors on tumors. However, the

mechanisms aecting oncogenic processes particularly in head and neck

squamous cell carcinomas (HNSCC) are not fully understood. e aim

was to identify the eects of ADORA2B (adenosine receptor A2B) on

HNSCC-derived cell lines.

Methods: First, the expression prole was analyzed by RT-PCR and West-

ern-Blot. Second, the eects of ADORA modulation by receptor ligands

on proliferation, migration, invasion and angiogenesis were investigated.

Also, the activity of ADORA2B was analyzed. In vitro experiments in-

volved MTT assays, scratch assays, transwell migration assays, VEGF-ELI-

SA and cAMP-Assays; in vivo experiments involved tumor xenogra on

chicken chorionallantoic membranes (CAM-Assay).

Results: Targeting ADORA2B with the inverse agonist/antagonist PSB-

603 leads to inhibition of proliferation, transmigration and VEGFA secre-

tion in vitro. At the molecular level, cell cycle arrest as well as the induc-

tion of the apoptotic pathway were found. In addition, shRNA-mediated

down-modulation of ADORA2B expression caused decreased prolifera-

tion. Moreover, in in vivo xenogra experiments, chemical and genetic

abrogation of ADORA2B activity impaired tumor growth associated with

decreased tumor vascularization.

Conclusions: We found that ADORA2B is upregulated and constitutively

active in HNSCC-derived cell lines. e receptor promotes cell growth,

migration and angiogenesis in vitro and in vivo. Our data suggest ADOR-

A2B being an important biomarker as well as an interesting therapeutic

target for treatment of HNSCC.

Reference:

1. Mello P de A, Coutinho-Silva R, Savio LEB. Multifaceted eects of extracellu-

lar adenosine triphosphate and adenosine in the tumor-host interaction and

therapeutic perspectives. Front Immunol 2017;8:1–17.

Disclosure Statement: Nothing to disclose.

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2018

329

Eects of Exosomes on B Cell Populations in Head and Neck

Squamous Cell Carcinoma (HNSCC)

Jan Christian Schröder; Sandra S. Jeske; Thomas K. Homann;

Cornelia Bruner; Marie-Nicole Theodoraki; Patrick J. Schuler

Department of Otorhinolaryngology, Head and Neck Surgery, University of

Ulm, Ulm, Deutschland

Purpose: e tumor microenvironment (TME) of HNSCCs is highly im-

munosuppressive. Tumor derived exosomes are key mediators of many

pro-tumorigenic eects and exhibit strong immunosuppressive proper-

ties. So far, this has been established for T cells and other leukocyte pop-

ulations, but the eects of exosomes on B cells remain to be elucidated.

Here we show that exosomes puried from the plasma of HNSCC patients

modify the phenotype of B cells.

Methods: : Exosomes were isolated from plasma of HNSCC patients by

mini size exclusion chromatography. B cells were puried from peripheral

blood of healthy donors by LeukoSep and CD19-negative selection and

co-cultured with HNSCC exosomes. Using ow cytometry, the expres-

sion of checkpoint receptors was determined. Adenosine production was

assessed by luciferase assay. e activity of the B cell receptor (BCR) path-

way was inferred by measuring the expression of phosphorylated Bruton’s

tyrosine kinase (p-BTK).

Results: Co-cultivation with HNSCC exosomes inhibited cluster for-

mation of stimulated B cells. is was accompanied by a decrease in the

expression of the co-stimulatory checkpoint receptor GITR and CD39,

an ATP-hydrolyzing ectoenzyme. In line with this, ATP hydrolysis and

adenosine production by exosome-treated B cells were decreased. Fur-

thermore, the expression of p-BTK was reduced.

Conclusions: ese results demonstrate that exosomes derived from HN-

SCC patients have direct eects on B cells in vitro. We suspect a global

inhibitory eect; since exosomes inhibited cluster formation; reduced the

expression of a co-stimulatory receptor and decreased the activity of the

BCR pathway.

387

Feasibility and Results of a Denitive Radiotherapy (RT) or

Chemoradiation (RCT) for Elderly Patients with Squamous Cell

Carcinoma of The Head and Neck (SCCHN) – a Retrospective

Monoinstitutional Survey

Matthias Hautmann 1; Anna Ratzisberger 2; Matthias Hipp 3; Felix Steger 1;

Tobias Ettl 4; Katja Evert 5; Oliver Kölbl 1; Christoph Süß 1

1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg, Deutschland

2Klinik für Psychiatrie, Bezirkskrankenhaus Passau, Passau

3Klinik für Strahlentherapie, Klinikum St. Marien, Amberg

4Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,

Universitätsklinikum Regensburg, Regensburg

5Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg

Purpose: SCCHN belong to the frequent malignancies worldwide. In an

aging society, also the incidence of SCCHN in elderly patients is rising.

Worldwide denitive RT or RCT is widely used as rst line therapy.

Nevertheless, elderly patients are underrepresented in clinical trials. e

aim of this survey was to evaluate the feasibility of a denitive RT/RCT

and the treatment results in a collective of elderly patients with SCCHN.

Methods: All patients older than 70 years, which received a denitive RT

or RCT at the University Hospital Regensburg from 2004 to 2018 were

included.

110 patients could be identied with a median age of 75 years. Most pa-

tients suered from a SCCHN UICC stadium IVa. 46 patients received a

concomitant chemoradiation, 64 patients were just irradiated. e median

pretreatment Karnofsky Performance Status was 70 %.

e median follow up was 16 months (IQR 7 to 30 months).

Results: e feasibility of radiotherapy was good. Only for 18 patients

radiotherapy had to be interrupted for more than one day. 46 % of the

patients could receive at least 75 % of the planned dose of the chemotherapy.

66 % of the patients suered from any acute toxicity of CTC grade III

or IV.

e overall survival was 59 % aer 12, 33 % aer 24 and 15 % aer 60

months. e local control was 85 % aer 12 months, 63 % aer 24 and 50

% aer 60 months.

Conclusions: We could nd a good feasibility of a denitive radiotherapy

and a reasonable feasibility of concomitant chemotherapy for elderly pa-

tients with SCCHN. Also in comparison with collectives of younger pa-

tients the overall survival is reasonable, particularly regarding the reduced

pretreatment general condition of the patients. Because of our results

concerning feasibility, a de-intensication of radiotherapy just due to age

seems not to be justied.

Disclosure Statement: On behalf of all authors, the corresponding author declares

that there are no conicts of interest.

397

The Role of Tertiary Lymphoid Structures in Adenoid Cystic

Carcinoma

Johannes Döscher 1; Simon Laban 1; Patrick J. Schuler 1;

Thomas K. Homann 1; Stephanie E. Weissinger 2

1Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie,

Universitätsklinikum Ulm, Ulm, Deutschland

2Institut für Pathologie, Universitätsklinikum Ulm, Ulm, Deutschland

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy of sali-

vary glands in the head and neck. e prognosis remains poor and late re-

currences oen occur aer 5 years and later.1 To date, there are no reliable

prognostic markers for ACC. In several solid tumors, tertiary lymphoid

structures (TLS) are associated with improved survival. is study aims to

investigate the role of distribution patterns of tumor inltrating immune

cells (TIL) in ACC.

Methods: Our screening cohort consisted of 10 ACC patients where for-

malin-xed paran embedded (FFPE) tissue of the primary tumor were

available. e validation cohort comprised further 25 patients. All patients

were treated at the Ulm University head and neck cancer center. Sections

were stained for CD3, CD4, CD8 and CD20 and evaluated with regard to

their distribution of TIL. Patterns were determined as inltrated-exclud-

ed, inltrated-inamed and presence of tertiary lymphoid structures as

published before.2

Results: In the screening cohort 8 of 10 tumors presented with an inl-

trated-excluded TIL pattern by inltrating ≤ 5% of the tumor. Two cases

showed an inltrated-inamed phenotype with more CD3+ cells (80%

and 60%) than CD20+ (20% and 40%) and additionally formed TLS.

ese two cases had no relapse, whereas 50% of the inltrated-excluded

tumors relapsed. Due to the limited case number in the screening cohort,

these results were not statistically signicant and are currently being veri-

ed in the validation cohort.

Conclusions: TIL patterns in ACC represent a promising prognostic tool

and could identify patients at risk of relapse. ese patients should be

monitored more closely and possibly treated more aggressively.

References:

1. Lloyd S et al. (2011) Determinants and patterns of survival in adenoid cystic

carcinoma of the head and neck, including an analysis of adjuvant radiation

therapy. Am J Clin Oncol Cancer Clin Trials 34:76–81.

2. Wagner D.-C. et al. (2018). [Prognostic signicance of immune cell inltrates

in tumor pathology]. Der Pathologe, 39(6), 532–538.

Disclosure Statement: Nothing to declare.

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2018

410

Feasibility and Results of a Postoperative Radiotherapy (RT) or

Chemoradiation (RCT) for Elderly Patients with Squamous Cell

Carcinoma of the Head and Neck (SCCHN) – a Retrospective

Monoinstitutional Survey

Christoph Süß 1; Anna Ratzisberger 1; Matthias Hipp 2; Felix Steger 1;

Tobias Ettl 3; Katja Evert 4; Oliver Kölbl 1; Matthias Günther Hautmann 1

1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,

Regensburg, Deutschland

2Klinik für Strahlentherapie, Gesundheitszentrum und Klinikum St. Marien

Amberg, Amberg, Deutschland

3Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,

Universitätsklinikum Regensburg, Regensburg, Deutschland

4Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg,

Deutschland

Purpose: SCCHN belong to the frequent malignancies worldwide. In an

aging society, also the incidence of SCCHN in elderly patients is rising.

Nevertheless, elderly patients are underrepresented in clinical trials. e

aim of this survey was to evaluate the feasibility of a postoperative RT/RCT

and the treatment results in a collective of elderly patients with SCCHN.

Methods: All patients older than 70 years, which received a denitive RT

or RCT at the University Hospital Regensburg from 2004 to 2018 were

included.

71 patients could be identied with a median age of 75 years. Most pa-

tients suered from a SCCHN UICC stadium IVa. 9 patients received a

concomitant chemoradiation, 62 patients were only irradiated.

e median follow up was 27 months (IQR 18 to 62 months).

Results: e feasibility of radiotherapy was good. Radiotherapy had to

be interrupted for more than one day for 18 patients. 6/9 patients could

receive at least 75 % of the planned dose of the chemotherapy.

52 % of the patients suered from any acute toxicity of CTC grade III

or IV.

e overall survival was 87 % aer 12, 67 % aer 24 and 41 % aer 60

months. We could only identify the pretreatment general condition as

predictive factor for overall survival.

e local control was 99 % aer 12 months, 88 % aer 24 months and 75

% aer 60 months.

Conclusions: We could nd a good feasibility of a postoperative RT or

RCT for elderly patients with SCCHN. Especially the local control was

quite satisfactory. ere seems to be no obvious dierence in overall sur-

vival in comparison with other collectives of younger patients or unselect-

ed patients regarding age. Our results show, that a de-intensication of

treatment just because of age seems not to be justied.

Disclosure Statement: On behalf of all authors, the corresponding author declares

that there are no conicts of interest.

446

Improved Detection of Promising Epigenetic Biomarkers

for Head and Neck Cancer in Saliva

Juliane Priese 1; Anna-Bawany Hums 2; Theresa Erler 2; Lars Jansen 3;

Matthias Dürst 3; Martina Schmitz 2; Orlando Guntinas-Lichius 1;

Alfred Hansel 2

1HNO-Klinik, Universitätsklinikum Jena, Jena, Deutschland

2oncgnostics GmbH, Jena, Deutschland

3Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,

Funktionsbereich „Gynäkologische Molekularbiologie“, Universitätsklinikum

Jena, Jena, Deutschland

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a het-

erogeneous disease. Two thirds of patients are diagnosed with advanced

tumour stages.1 erefore, we currently conduct a feasibility study with

the aim to prove that our validated cancer-specic markers, detected in

DNA from primary tumour tissue, may also be detectable in non-invasive

saliva samples.

Methods: HNSCC-specic DNA methylation markers (Z1-Z5; reference

ACTB) were validated using fresh-frozen tissue samples (20x HNSCC;

20x controls) by methylation-specic multiplex QPCR on the cobas z 480

analyzer (Roche). e aim is to include 200 patients in the study. For mul-

tiplex QPCR testing both, tissue and saliva are collected from each HN-

SCC patient at the Department of Otorhinolaryngology, Jena University

Hospital. Isolated genomic DNA is bisulte-converted before use.

Results: Validation of Z1 – Z5 by multiplex QPCR yielded 100% clinical

sensitivity and 95% specicity, if 1/5 markers were positive, in HNSCC

and control tissues. Single marker sensitivity ranged from 30% to 70%

and specicity from 95% to 100% in this validation sample set. In samples

collected from the rst six HNSCC patients, the markers Z1, Z3-Z5 were

detected in the six available tissue samples. Z1 showed matching results

between all six tissue and saliva samples. Z5 showed positive detection

in 6/6 tissue and 5/6 saliva samples. Z2 – Z4 had weak detection rates in

saliva samples so far. Results from the control group are not yet available.

Conclusions: Preliminary results support our study hypothesis to

robustly detect HNSCC markers in both, tissue and saliva. Utilization of

saliva samples for cancer-specic diagnostic assays based on epigenetic

markers will be useful in in vitro diagnostics aiming at secondary and

tertiary prevention.

Reference:

1. Gatta G, et al. Eur J Cancer 2015; 51(15):2130-2143

Disclosure Statement: is study was supported by oncgnostics GmbH; Jena;

Germany.

474

Eects of Decitabine on the Expression of Immune

Checkpoints Molecules (ICM)

Adrian Fehn 1; Jasmin Ezic 1; Cornelia Brunner 1; Sandra Jeske 1;

Lisa Puntigam 1; Johannes Döscher 2; Patrick J. Schuler 2;

Thomas K. Homann 2; Simon Laban 2

1HNO-Klinik der Universität Ulm, Forschungslabor, Ulm, Deutschland

2HNO-Klinik der Universität Ulm, Ulm, Deutschland

Purpose: Decitabine (DAC) reduces DNA methylation unspecically.

DNA demethylation increases the expression and repertoire of cancer-tes-

tis antigens (CTA) in cancer cells, potentially enhancing immunogenicity.

DAC eects on immune cell (IC) phenotype and function in the tumor

microenvironment need to be taken into consideration. To this end, we

set out to characterize DAC induced changes in IC.

Methods: Peripheral blood mononuclear cells (PBMC) of patients with

oropharyngeal carcinoma and healthy controls were cultivated and treat-

ed at 1µmol/l for 5 consecutive Days. Changes in ICM expression were

analyzed by ow cytometry. Four panels were designed with ve backbone

markers (CD3,4,8,39,19) each. Expression of ICMs (PD-1, CTLA4, BTLA,

CD137, CD27, GITR, LAG-3, OX40, TIM3, VISTA, ICOS, TIGIT) was

analyzed. Cytotoxicity was monitored with Annexin V / 7AAD staining

plus CD3,4,8,39&19.

Results: Variations in dierent immune cell populations’ susceptibility to

DAC’s cytotoxicity were observed. CD19+ B cells were depleted by 78%,

CD39+ cells were depleted by 29%, CD8+ cells increased by 19% and

CD4+ cells by 38% compared to control treated cells. DAC evokes a shi

in the expression pattern of immune checkpoint molecules: In healthy

controls DAC reduced the expression of PD1 and CTLA4 in CD4+ cells,

whereas tumor patients showed increased expression of these ICMs in

CD8+ and CD4+ cells. CD19+ cells show an increase in OX40 and de-

crease in CD27 expression. CD39+ cells show decreased levels of PD1,

CD137, CD27, ICOS and TIGIT.

Conclusions: DAC treatment alters the expression of ICM and lympho-

cyte subpopulations proportions. is needs to be considered when com-

bining DAC with immunotherapy. Further experiments are ongoing to

validate and extend our ndings.

Disclosure Statement: P.J.S.: Advisory Boards: BMS; MSD. T.K.H.: Advisory

Boards: MSD; BMS; MSD. Honoraria: Merck Serono; BMS. S.L.: Advisory Boards:

Merck Sharp & Dohme (MSD); Bristol Myers Squibb (BMS); Astra Zeneca (AZ).

Honoraria: MSD; BMS; AZ; Merck Serono. All other authors indicated no poten-

tial conict of interest.

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475

Cell-Free DNA in Plasma or Saliva for Minimally Invasive

Monitoring of Head and Neck Cancer Patients

Romina Roesch 1, 2; Irina Kerle 2; Markus Wirth 3, 4; Markus Nieberler 5;

Nicole Pfarr 6; Carolin Mogler 6; Fabian Stögbauer 6; Philipp Blüm 2;

Silvia Thoene 1, 4; Ramona Secci 1, 4; Andreas Bietenbeck 1; Sara Krippgans 5;

Jakob Rinecker 3; Christoph Straube 4, 7; Clemens Heiser 3;

Klaus Dietrich Wol 5; Wilko Weichert 4, 6; Stephanie Combs 4, 7;

Florian Bassermann 2, 4; Jürgen Ruland 1, 4; Christof Winter 1, 4

1Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der

Technischen Universität München , München, Deutschland

2III. Med. Klinik für Hämatologie und Onkologie, Klinikum rechts der Isar der

Technischen Universität München, München, Deutschland

3Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Klinikum rechts der

Isar der Technischen Universität München, München, Deutschland

4DKTK Partnerstandort München, Deutsches Krebsforschungszentrum (DKFZ)

Heidelberg

5Klinik und Poliklinik für Mund- Kiefer- Gesichtschirurgie, Klinikum rechts der

Isar der Technischen Universität München, München, Deutschland

6Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische

Universität München, München, Deutschland

7Klinik und Poliklinik für RadioOnkologie und Strahlentherapie, Klinikum rechts

der Isar der Technischen Universität München, München, Deutschland

Purpose: In patients with head and neck cancer (HNC), disease

monitoring and recurrence detection are currently based on clini-

cal examination and imaging. Liquid proling of tumor-derived nu-

cleic acids such as cell-free tumor DNA (ctDNA) in plasma and in sa-

liva could provide better monitoring and earlier recurrence detection.

Here, we aim is to determine to which extent ctDNA and HPV DNA can

be detected in plasma and saliva, and which sample material is more suit-

able for liquid-based HNC proling.

Methods: In 92 HNC patients, blood plasma and saliva samples were pro-

spectively collected aer surgery and analyzed with digital droplet PCR

(ddPCR) assays to detect two TERT promoter hotspot mutations. In the

subgroup of 50 patients with HPV-associated tumor localizations, cell-

free DNA (cfDNA) was tested for HPV16 (E7) in plasma and saliva. To

increase the detection rate, mutations in the primary tumor were iden-

tied with NGS (45 genes) and ctDNA was quantied using individually

designed mutation-specic ddPCR assays.

Results: In 33% (30/92), ctDNA was detected in plasma, in 38% al-

ready in early tumor stages (I/II). In saliva, ctDNA was detected in 52%

(17/33). In the course of disease, a tumor progression could be detect-

ed by increasing ctDNA concentrations in plasma or saliva on aver-

age 5 months (2 weeks to 13 months) earlier than by clinical imaging.

In p16-pos. patients (n=16), HPV16 cfDNA was detected in plasma in

39% (6/16), in 50% already in early tumor stages (I/II). P16-pos. HPV-

neg. patients (10/16) showed an unfavorable clinical course compared to

p16-pos. HPV-pos. patients (30% died, 79% had a relapse or progressive

disease).

Conclusions: Liquid proling with ddPCR-based detection of ctDNA

in blood and saliva is a promising tool for disease monitoring and early

recurrence detection in HNC patients. In HPV-associated tumors, HPV

cfDNA could be a complementary marker for disease monitoring and for

identifying a subgroup of p16-pos. tumors that are not driven by HPV

infection.

Disclosure Statement: no conict of interest

545

Intrathecal Ziconotide and Morphine Using Cervical Catheters

for Cancer Analgesia

Denis Dupoiron; Gabriel Carvajal; Francois Boré; Pierre Yves Dubois;

Damien Leblanc; Sabrina Jubier Hamon; Thierry Delorme;

Virginie Jaoul; Nathalie Lebrec

institut de cancérologie de l‘ouest , ANGERS, Frankreich

Purpose: Pain remains the rst symptom in cancer population at an ad-

vance stage of the disease (1). Intrathecal drug delivery systems (IDDS) is

ecient to relieve pain refractory to comprehensive medical management

(2). However, IDDS through cervical catheters with Ziconotide for Head

and Neck Cancer (HNC) pain is a new option never described on litera-

ture. is prospective follow up study was designed to evaluate results of

cervical IDDS with Ziconotide for Cancer pain at the ICO.

Methods: Patients were treated from 2010 to 2017, aer selection for

IDDS based on multidisciplinary meeting discussion. Aer a complete

withdrawal of systemic opioids, IDDS-treated patients were prescribed

a combined intrathecal regimen (morphine, ropivacaine and ziconotide)

through a catheter placed behind the cervical spinal cord. Post-implant

assessment of pain was determined using a numeric rating scale (NRS).

Results: 43 patients were included from 2010 to 2017, total therapy du-

ration accounts for 9013 IDDS-days. Implanted patients suered from

severe pain (mean presurgical NRS 8.6±0.8) despite a mean 566 +/-112

mg oral morphine equivalent daily dose. Median survival time aer IDDS

was 125 ± 176 days. IDDS provided great pain relief with signicant dif-

ference (p < 0.01) aer 1 week (2.4+/- 0,46), 1 month (2.7 +/- 0,44) and 2

months (2.8+/- 0.55) 50%. Only one serious adverse eect was observed

with ziconotide.

Conclusions: Long-term IDDS using a multidrug regimen including

ziconotide for HNC pain through cervical intrathecal catheters reduce

pain scores and seems safe in our study population, using mainly a percu-

taneous lumbar approach.

References:

1. van den Beuken: Update on Prevalence of Pain in Patients With Cancer -

JPSM. 2016;51(6)

2. Smith TJ: Randomized clinical trial of IDDS -JCO 2002;20(19)

Disclosure Statement: Dr Dupoiron is consultant for Medtronic and RIEMSER

Pharma GmbH.

595

Expression of the Immune Modulators of the PD-1: PD-L1 Axis

in oral Leukoplakia

Jutta Ries 1; Falk Wehrhan 1; Christoph Baran 1; Abbas Agaimy 2;

Eva Danzer 1; Stella Bolze 1; Maike Büttner-Herold 2; Marco Kesting 1;

Manuel Weber 1

1Mund-, Kiefer und Gesichtschirurgische Klinik, Unversitätsklinikum Erlangen,

Erlangen, Deutschland

2Pathologie, Unversitätsklinikum Erlangen, Erlangen, Deutschland

Purpose: PD/PD-L1 Immune Checkpoint overexpression is involved in

immunosuppression and the failure of an immune response against tumor

cells. Cancer immunotherapy using antibodies targeting this axis has be-

come a new therapeutic approach also for patients suering from OSCC.

Little is known about its expression in oral precancerous lesions like oral

leukoplakia (OLP). e aim of the study was to check whether altered PD/

PD-L1 expression already exists in OLP and whether it is associated with

malignant transformation.

Methods: PD-1 and PD-L1 expression were immunohistologically an-

alyzed separately in the epithelium and the subepithelium of OLP that

transformed malignant within 5 years (T-OLP), in OLP without malig-

nant transformation (N-OLP), in corresponding OSCC and in healthy

oral mucosa (NOM). Additionally, RT qPCR analysis for PD-L1 expres-

sion was done in the entire tissues. e expression rates were compared

and statistical signicance of the expression change between the groups

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and the association between overexpression and malignant transforma-

tion was determined.

Results: PD-1 was overexpressed in the epithelial and subepithelial com-

partment of T-OLP compared to N-OLP (PE=0.001; PS=0.005). No signif-

icant dierence in PD-L1 mRNA expression between transforming and

non-transforming OLP could be demonstrated (P=0.10). However, the

PD-L1 protein was signicantly overexpressed in the epithelial section of

transforming OLP (p=0.007), but not in the subepithelial compartment

(p=0.25) compared to N-OLP. Additionally, this overexpression was sig-

nicantly associated to malignant transformation within 5 years.

Conclusions: PD-1/PD-L1 may represent a prognostic indicator to deter-

mine the risk of malignant progression of OLP. Local immunosuppression

in the epithelium could be induced by PD-L1 overexpression in epithelial

cells and trigger malignant transformation. Hence, checkpoint inhibitors

could counteract tumor development and serve as therapeutic agents in

patients with high-risk OLP lesions.

600

Zoledronate Shifts Macrophage Polarization towards M1

in Vivo - An Animal Study on Wistar Rats

Manuel Weber 1; Kerstin Amann 2; Andi Homm 3; Stefan Müller 3; Jutta Ries 1;

Carol Geppert 4; Raimund Preidl 1; Marco Kesting 1; Falk Wehrhan 1

1Mund-, Kiefer- und Gesichtschirurgische Klinik Erlangen, Erlangen,

Deutschland

2Pathologisches Institut, Nephropathologische Abteilung, Erlangen,

Deutschland

3Erlangen, Mund-, Kiefer- und Gesichtschirurgische Klinik, Erlangen,

Deutschland

4Pathologisches Institut, Erlangen, Deutschland

Purpose: Clinical studies and in vitro analyses indicate that immunomod-

ulatory properties of bisphosphonates contribute to the development of

medication associated osteonecrosis of the jaw (MRONJ) as well as to the

anti-metastatic eect observed in certain groups of breast cancer patients.

Macrophages are precursor cells of osteoclasts and could be potential can-

didates for the mediation of immunological eects of bisphosphonates.

Aim of the study was to investigate the inuence of zoledronate on density

and polarization of macrophages in dierent tissues of the Wistar rat.

Methods: A total of 120 animals (6-month-old male Wistar rats) were

divided into 4 groups, 56 of which were treated with 8x 40mg/kg body

weight zoledronate i.p. Aer 2, 4 and 8 weeks the tissues skin, lung, spleen

and tongue were removed and immunohistochemically examined for the

expression of CD68, CD163 and iNOS positive cells using a tissue mi-

croarray.

Results: In bisphosphonate treated animals a signicantly increased mac-

rophage cell count (increased CD68 expression) as well as signicantly

increased iNOS expression and signicantly decreased CD163 expression

was observed.

Conclusions: Bisphosphonate application leads to a shi of macrophage

polarization towards M1 in vivo. is provides a possible explanation for

the clinically observed anti-tumor eect of bisphosphonates.

Disclosure Statement: e authors declare no conict of interest.

632

A Randomized Phase II Study on the Optimization of

Immunotherapy in Squamous Carcinoma of the Head and

Neck (SCCHN) – OPTiM (AIO-KHT-0117)

Viktor Grünwald 1; Dennis Hahn 2; Jürgen Alt 3; Justin Hasenkamp 4;

Konrad Klinghammer 5; Gunter Schuch 6; Gunnar Hapke 7; Philipp Ivanyi 8

1Universitätsklinikum Essen, Innere Klinik, Essen, Deutschland

2Klinikum Stuttgart, Klinik für Hämatologie, Onkologie und Palliativmedizin,

Stuttgart, Deutschland

3Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III.

Medizinische Klinik und Poliklinik, Mainz, Deutschland

4Universitätsmedizin Göttingen, Georg-August-Universität, Hämatologie und

Onkologie, Göttingen, Deutschland

5Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Medizinische

Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,

Berlin, Deutschland

6HOPA - Hämatologisch-Onkologische Praxis Altona, Hamburg, Deutschland

7Kath. Marienkrankenhaus Hamburg gGmbH, Hamburg, Deutschland

8Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,

Onkologie und Stammzelltransplantation, Hannover, Deutschland

Purpose: e OPTIM trial investigates whether dual checkpoint block-

ade is superior to docetaxel chemotherapy as early salvage therapy in re-

current or metastatic SCCHN (R/M-SCCHN). e primary endpoint is

overall response rate aer randomization, hypothesizing that dual check-

point blockade improves ORR to 25% compared to 10% with docetaxel.

Secondary endpoints are overall survival, progression-free survival, safety,

and quality of life.

Methods: 280 patients with R/M-SCCHN progressing aer plati-

num-based chemotherapy or within 6 months aer RCT will initially re-

ceive nivolumab monotherapy (240 mg Q2W). ey are closely followed

for tumor progression by radiologic assessment at increased frequency

(i.e. every 4-6 weeks). Patients who progress during the rst 24 weeks of

nivolumab monotherapy are randomized 1:1 between intensied immu-

notherapy (nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg Q6W) and

chemotherapy (docetaxel 75 mg/m2 Q3W). 154 patients are planned to

be randomized. Patients who do not progress continue nivolumab mono-

therapy according to standard of care. Aer randomization, study treat-

ment continues until disease progress or for up to 12 months.

Results: Recruitment started in July 2018 and is ongoing. Results will be

published aer nalization of study.

Disclosure Statement: All authors have no relevant nancial or nonnancial

relationships to disclose.

OPTIM (EudraCT 2017-003349-14) study sponsor is AIO-Studien-gGmbH;

Berlin. e study is nancially supported by Bristol-Myers Squibb.

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Health Economy/Public Health

Vorträge

421

Health Economic Eects of Biosimilars: The Potential for the

Long-Term Financing of Oncological Care and Therapeutic

Innovations

Michael Patrick Lux 1; Florian Kron 2, 3; Kai Hübel 2

1Kooperatives Brustzentrum Paderborn, Klinik für Gynäkologie und

Geburtshilfe, Frauen- und Kinderklinik St. Louise, Paderborn, Deutschland

2University of Cologne, Faculty of Medicine and University Hospital of Cologne,

Dept. I of Internal Medicine, Köln, Deutschland

3FOM University of Applied Sciences, Essen, Deutschland

Purpose: Several new options for individualized and targeted therapies

in oncology and immunology are available or in development. However,

these are cost intensive, in particular in view of healthcare systems with

limited resources. Hence, new nancing approaches are warranted. Bio-

similars are biological drugs containing the active substance of an already

approved reference biological drug. e introduction of biosimilars can

relieve the burden on healthcare and thus nance new therapies. How-

ever, existing data shows that the saving potential in Germany is far from

exhausted.

Methods: Based on available health economic analyses, the actual use and

eects of biosimilars were determined using the examples of trastuzumab,

rituximab and G-CSF. e associated costs of the originator and biosimi-

lar were compared to determine the saving potential in the real world for

the German healthcare system. Incidence calculations were based e.g. on

data from the Robert-Koch-Institution, Munich cancer registry, quality

indicators of the certied centers and calculations of the IQWiG benet

assessments. Cost calculation was based on Lauer tax (15/12/2018).

Results: According to the example of trastuzumab and calculations based

on various sources, the number of patients with HER2-positive breast

cancer receiving trastuzumab in the adjuvant and metastatic setting

ranges from 8,199 to 14,380 and 4,643 to 4,670 cases/year, respectively.

is corresponds to a range of 118,745 to 208,250 cycles/year in the ad-

juvant setting and 236,793 to 238,170 cycles/year in the metastatic set-

ting. e annual saving potential would amount from 87,883,705 EUR to

120,496,027 EUR if all patients received the least expensive trastuzumab

biosimilar compared to the original drug.

Conclusions: e available data show that potential savings are far from

exhausted and that, if the option of biosimilars is fully exploited, enor-

mous resources can be released in the healthcare system in order to oset

nancing new innovative forms of therapy. Additional calculations for rit-

uximab and G-CSF will be provided.

Poster

Assessment of Metastatic Colorectal Cancer Patient

Preferences for Biologic Treatments in Germany Using a

Discrete Choice Experiment – Study in Progress

Moushmi Singh 1; Robert Bartsch 2, 2; Anna-Maria Stegherr 3;

Fränce Hardtstock 4; Margit Hemetsberger 5; Andrea Lebioda 2

1Health Economics, Amgen Ltd., Uxbridge, United Kingdom

2Value, Access & Policy, Amgen GmbH, Munich, Deutschland

3Medical Aairs, Amgen GmbH, Munich, Deutschland

4Ingress-Health HMW GmbH, Wismar, Deutschland

5Hemetsberger medical services, Wien, Österreich

Purpose: is is an ongoing discrete choice experiment (DCE) that aims

at understanding patient preferences in the systemic biologic treatment of

metastatic colorectal cancer (mCRC), focusing on the perception of ad-

verse event risk relative to the expected treatment benets.

Methods: is ongoing multicenter cross-sectional study is a based on

patient interviews using a DCE framework. It aims to include 150 patients

with mCRC from 15-20 sites in Germany. It includes adult patients (≥18

years) with a physician-reported diagnosis of mCRC actively or previous-

ly (within the previous 3 months) receiving or about to be initiated on a

rst-line mCRC therapy. All participants must provide written informed

consent. Patients are asked to make several stated (hypothetical) choices

in deciding between two alternative treatment options to quantify their

preferences for dierent mCRC treatment attributes, specically attri-

butes related to ecacy (e.g., overall survival) in relation to safety (e.g.,

risk of rash, infusion reactions, or gastrointestinal hemorrhage).

Results: is study is currently recruiting patients and results are expected

in December 2019. In a conditional logit regression model, the inuence

of dierent attribute levels on the probability of a patient’s choice for or

against a specic treatment alternative will be estimated. In an additional

analysis, utility values will demonstrate marginal willingness to accept a

given attribute if a specic treatment with a more favorable attribute level

could be received. Furthermore, relative importance of each attribute for

the overall decision for or against an option in the DCE will be provided.

Additionally, a latent class analysis to identify and describe patient sub-

groups will be done.

Conclusions: ere is a lack of research focusing on patient preferences

with a biological mCRC treatment and there are no existing data for Ger-

many so far. erefore, this study will facilitate a better understanding of

trade-os related to the existing treatment of the disease from the per-

spective of the German population.

Development of a Telemedical Software for the Organisation

of Oncological Councils and Tumor Conferences within the

Project “Tumornetzwerk Sachsen“

Sonja Hiemer 1; Sybil David 2; Axel Petzka 2; Nicole Lakowa 2

1Tumornetzwerk Sachsen/Onkologisches Zentrum St. Georg, Klinikum St. Georg

Leipzig, Leipzig, Deutschland

2Tumornetzwerk Sachsen, Klinikum St. Georg Leipzig, Leipzig, Deutschland

Purpose: Strategies for Cancer patients need to be discussed within in-

terdisciplinary tumor conferences. e development of the soware “eTu-

morkonsil” for telemedical consultation of oncological patients will allow

physicians of various disciplines and medical facilities to network digitally

wherever located. is will improve the medical care of cancer patients,

also for patients in structurally weak areas.

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Methods: e application “eTumorkonsil” is going to be developed on an

established telemedicine platform and will allow physicians to share onco-

logical councils using electronical (e-) councils or to take part in e-tumor

conferences, two possible functions within the soware. Furthermore, all

clinical information will be made available directly to a digital patient re-

cord. e user of the application, dened by a login, may request second

opinions on oncological issues and discuss patients digitally using a high

quality phone and video conferencing system. e program is web based

and therefore capable of running independent and free of any connection

into operating systems.

Results: Uniform processes ensure a fast procedure of the digital councils

without media disruption. e transmitted patient data is encrypted in

agreement with the data protection requirements. e application is user

friendly, so that the preparation and follow-up as well as the execution

of the tumor conference are logically organized. erapy recommenda-

tions are provided on the platform by standardized digital paths within

24 hours.

Conclusions: In the Free State of Saxony physicians who are responsible

for outpatient and inpatient treatment are able to be networked with the

telemedical application “eTumorkonsil” in a multidirectional way. Hereby

it is possible to optimize the care of cancer patients; especially in structur-

ally weak regions; by connecting them to certied cancer centers. „eTu-

morkonsil“ oers an innovative and time-ecient support in oncological

care for everyday medical practice and stand for a continuous quality as-

surance in the context of patient care.

230

Measuring Utilities in Cancer Patients - The EORTC QLU C10D

Matthias Büttner 1; Eva Gamper 2; Georg Kemmler 2

1Universitätsmedizin Mainz, Institut für Medizinische Biometrie, Epidemiologie

und Informatik, Mainz, Deutschland

2Medizinische Universität Innsbruck, Department für Psychiatrie und

Psychotherapie, Innsbruck, Österreich

Purpose: Health economic analysis and therefore cost-utility studies are

becoming more prominent in cancer research. Generic utility instruments

may not address cancer patients in a suitable way due to the complexity

of the disease [1]. e EORTC QLU C-10D is a new multi-attribute utility

instrument derived from the cancer-specic EORTC QLQ C-30, which

is one of the most widely-used quality of life instruments for assessing

cancer patients’ quality of life. e aim of this project was to develop can-

cer-specic utility weights derived from the EORTC QLQ C-30 for ve

European countries.

Methods: A professional marketing company set up the DCEs with a gen-

eral population of 1000 participants in each country. Discrete Choice Ex-

periments (DCEs) from a general population in ve European countries

(Austria, Germany, France, Italy and Poland) were used to derive utilities

from the C-30. e key dimensions used for the discrete choice experi-

ments have been identied in previous studies.

Results: e dimension that impacted most on choice was physical func-

tioning followed by pain for all ve European countries. Regarding the or-

der of impact for the other dimensions, slight variations were seen across

the countries. Relevant cancer-related symptoms with a moderate eect

were nausea and bowel problems. A small impact across all ve European

countries was seen for fatigue, sleep problems, and appetite loss. e high-

est utilities were seen for Italy, while the lowest were obtained for France.

Conclusions: is project provided the rst country-specic European

utility weights for the QLU C-10D in ve EU countries. ese utilities can

be applied in future clinical trials using the EORTC QLQ C-30. Further

valuations for European and Asian countries are performed.

Reference:

1. Pickard AS, Ray S, Ganguli A, Cella D. Comparison of FACT- and EQ-5D-ba-

sed utility scores in cancer. Value Health. 2012;15(2):305-11.

Disclosure Statement: e authors have nothing to disclose.

751

Time-Dependent Risk Predictions As Novel Method

to Improve Screening Eciency

Vinzenz Völkel 1, 2; Teresa Draeger 1, 2; Sabine Siesling 3; Hendrik Kojberg 3

1Caritas Krankenhaus St. Josef, Regensburg, Deutschland

2Tumorzentrum Regensburg, Regensburg, Deutschland

3Universität Twente, HTSR, Enschede, Niederlande

Purpose: Risk-prediction tools allow to classify patients into risk-groups

based on risk thresholds. e usage of information concerning an indi-

vidual’s risk development over time would facilitate further tailoring of

screening schemes.

Methods: In a simulation analysis, three screening approaches (risk-

based, time-independent: cumulative approach CA; risk-based, time-de-

pendent: cumulative approach with interval-specic reevaluation CAIR,

interval-specic approach ISA) are compared regarding their impact on

screening-eciency. For this purpose, 81 scenarios featuring 5,000 pa-

tients with time-dependent risk estimations for a hypothetical disease D

and ve consecutive intervals of one year are simulated, using dierent

parameters to model disease progression, risk-distribution, risk-correla-

tion, and target detection rate of screening (tdr). e results of these sim-

ulation analyses are validated using a real-world clinical case-study based

on German breast cancer patients and the INFLUENCE-nomogram for

locoregional breast cancer recurrence.

Results: If individual, time-dependent risk estimations were used to per-

sonalize screening at a xed tdr of 90%, the percentage of saved screen-

ing examinations relative to an uninformed approach could exceed 20%,

depending on the simulated scenario. Whereas the time-independent

approach CA is associated with acceptable saving potentials in case of a

relatively homogenous risk distribution, the time-dependent approaches

CAIR and ISA are superior when risk-variation increases. With slowly

progressing diseases, approach CAIR yields the highest eciency on pop-

ulation level, for rapidly progressing diseases, approach ISA is superior.

e possible benets of time-dependent risk-based screening were con-

rmed in the real-world clinical case-study.

Conclusions: An appropriate usage of time-dependent risk-predictions

may considerably enhance screening eciency. erefore; predicting risk

development over time should be incorporated in future prediction-tools

and decision-algorithms.

771

Gera: a Health Economic Trial to Analyze the Impact of eHealth

in Breast Cancer Care

Tanja Eggersmann 1; Christoph Riese 2; Claudia Wenzel 2; Timo Schinköthe 2;

Tom Degenhardt 1; Rachel Würstlein 1; Nadia Harbeck 1; Manfred Welslau 3

1Breast Center, University Hospital Munich, Department of Gynecology and

Obstetrics, CCC of LMU, München, Deutschland

2CANKADO, Kirchheim bei München, Deutschland

3Hematological-Oncological Practice, Hospital Aschaenburg, Aschaenburg,

Deutschland

Purpose: In breast oncology, the increasing number of oral drug therapies

poses great challenges for patient management. Numerous studies

demonstrate that well-informed patients develop higher condence

in their treatment and a greater sense of disease control, resulting in

increased adherence and persistence as well as potentially better outcome.

e electronic Patient Reported Outcome (ePRO) tool CANKADO is

designed to help oncologists to bridge the gap between good, personalized

care and a time and resource-saving treatment for cancer patients.

Methods: Aim of GERA is to assess the economic impact of an ePRO tool

in breast cancer care. It is a prospective, single arm, non-interventional

trial, based on questionnaires that answered by patients via the CAN-

KADO Patient App. All patients undergoing systemic therapy for breast

cancer with access to CANKADO will be included in the evaluation. is

study will take place in 10 German centers and 337 patients will be includ-

ed in the study. e enrollment phase of patients will last 6 months, while

the individual patient observation and accompaniment phase through

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CANKADO will continue for 3 months. Primary objective is to gain

knowledge on the health economic impact of CANKADO resource uti-

lization in breast cancer care including the evaluation of physicians’ time

and patient experience. As secondary objectives, exploratory analysis of

all collected information is planned. is includes the socio-demograph-

ic patient information, clinical characteristics, quality-of life and patient

documentation behavior.

Results: e GERA trial is ongoing. Results will be presented at the con-

ference.

References:

1. Eggersmann TK, Harbeck N, Schinkoethe T, Riese C. eHealth solutions for

therapy management in oncology. Breast Cancer Management vol.6, no.3,

special report (2018), Future medicine. https://doi.org/10.2217/bmt-2017-0005

2. Schinkothe T. Individualized eHealth Support for Oncological erapy Ma-

nagement. Breast care (Basel, Switzerland), 2019;14:130-4.

Disclosure Statement: None declared

Imaging

Poster

288

A Deep Learning-Based Pipeline for The Automation of the

HER2 Gene Amplication Status Detection on Digitalized

Whole Fluorescence in Situ Hybridization (Fish) Slides in

Breast and Gastric Cancer

Falk Zakrzewski 1; Sarah Schmell 1; Walter De Back 2; Martin Weigert 3, 4;

Torsten Wenke 5; Silke Zeugner 1; Robert Mantey 6; Christian Sperling 1;

Ingo Röder 2, 6; Daniela Aust 1, 6; Pia Hönscheid 1, 6; Gustavo Baretton 1, 6

1Institut für Pathologie des Universitätsklinikums Carl Gustav Carus, Dresden,

Deutschland

2Technische Universität Dresden, Dresden, Deutschland

3Center for Systems Biology Dresden, Dresden, Deutschland

4Max-Planck-Institut für molekulare Zellbiologie und Genetik, Dresden,

Deutschland

5ASGEN GmbH & Co. KG, Dresden, Deutschland

6Nationales Centrum für Tumorerkrankungen (NCT) Dresden, Dresden,

Deutschland

Purpose: e human epidermal growth factor receptor 2 (HER2) gene

amplication status is important for therapy assessment in breast and gas-

tric cancer. It is visually assessed by pathologists based on FISH imaging

using a uorescence microscope or uorescence scanner. To automatize

this daily clinical routine in terms of speed, accuracy and objectivity, a

multi-step deep learning (DL) based pipeline was developed to mimic the

evaluation steps performed by pathologists.

Methods: e DL pipeline relies on (1) the prediction of the image-wide

HER2 gene amplication status via image classier convolutional neural

networks (CNNs), (2) the detection, localization and classication of in-

terphase nuclei and their HER 2 and CEN17 uorescence signals based on

(2a) object detection and (2b) pixel-wise segmentation networks and (3)

the visualization of the decision making of the networks to enable inter-

pretability by pathologists.

Results: We demonstrate that the accuracy of our DL pipeline is on par

with a team of pathologists for the classication of whole FISH slides.

Moreover, by classifying each nucleus independently by dierent net-

works, our system provides deep medical reports increasing both robust-

ness and interpretability.

Conclusions: Our pipeline is a large step in automating the evaluation of

the HER2 status of tumors using whole FISH slide scans and in optimiz-

ing the documentation of each tumor sample by automatically annotating

and reporting of the HER2 gene amplication status. is system is in

principle also transferable to all current FISH-based analyses which are

routinely performed at pathology institutes.

Disclosure Statement: Falk Zakrzewski, Martin Weigert and Torsten Wenke are

founders of the startup company ASGEN.

519

Sodium MRI at 7 Tesla as a Potential Biomarker for Tumor

Inltration and IDH Status in Glioma Patients

Sebastian Regnery 1, 2; Nicolas Behl 3; Tanja Platt 4; Nina Weinfurtner 5;

Katerina Deike-Hofmann 5; Felix Sahm 6, 7; Mark E. Ladd 4, 8;

Heinz-Peter Schlemmer 5; Jürgen Debus 1, 2; Stefan Rieken 1, 2;

Daniel Paech 5; Sebastian Adeberg 1, 2

1Heidelberg University Hospital, Department of Radiation Oncology,

Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation

Oncology, Heidelberg, Deutschland

3Siemens Healthineers, Erlangen, Deutschland

4German Cancer Research Center (DKFZ), Division of Medical Physics in

Radiology, Heidelberg

5German Cancer Research Center (DKFZ), Division of Radiology, Heidelberg

6Heidelberg University Hospital, Department of Neuropathology, Heidelberg

7German Cancer Research Center (DKFZ), Clinical Cooperation Unit

Neuropathology, Heidelberg

8University of Heidelberg, Faculty of Physics and Astronomy and Faculty of

Medicine, Heidelberg

Purpose: ese are the rst data from a prospective trial investigating so-

dium (23Na) MRI at 7 Tesla (T) as a potential biomarker for tumor inltra-

tion and isocitrate dehydrogenase (IDH) mutation.

Methods: 30 glioma patients underwent 23Na MRI on a 7 T scanner (Sie-

mens Healthineers, Erlangen, Germany) parallel to standard 3T MRI

before chemoradiation. A self-developed density-adapted 3D radial pro-

jection pulse sequence [1] with consecutive iterative 3D-DLCS recon-

struction [2] was employed. Areas of gadolinium contrast enhancement

(gdce), non-enhancing T2 hyperintensity (regarded as edema) as well

as necrosis were segmented, and regions of interest were placed inside

normal-appearing white matter (nawm) on 3T MRI. All segmentations

were registered to the 23Na images in MITK (http://mitk.org). e median

23Na signal of all areas was compared by pairwise t-tests, and the dier-

ence in median 23Na signal of the whole tumor was compared between

IDH-mutated (mut, N=6) and IDH-wild-type (wt, N=18) gliomas by a

Mann-Whitney U test.

Results: e 23Na signal increased successively from nawm to necro-

sis (mean ± sd [mM]: nawm = 37.8 ± 5.9, edema = 54.7 ± 10.6, gdce =

61.7 ± 13, necrosis = 81.9 ± 17.5) and the signal dierences between all

areas proved signicant (p-values for all pairwise comparisons < 0.01).

Furthermore, IDH-mut gliomas showed signicantly higher 23Na signal

than IDH-wt gliomas (median (interquartile range) [mM]: wt = 52.4 (46

– 58.6), mut = 65 (58.9-67.1), p = 0.0094).

Conclusions: e continuous gradient of 23Na signal from central necro-

sis to white matter suggests a correlation with tumor inltration. Consid-

ering the additional correlation with IDH status, 23Na MRI could enhance

identication of biopsy sites and assist image-guided surgery and radio-

therapy.

References:

1. Nagel et al., e potential of relaxation-weighted sodium magnetic resonance

imaging as demonstrated on brain tumors. 2011.

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2. Behl et al., ree-dimensional dictionary-learning reconstruction of (23)Na

MRI data. 2016.

Disclosure Statement: N.G.R.B. currently works for Siemens Healthineers.

641

Development of a Convolutional Neural Network (CNN)-Based

Classier for Automated Tissue and Tumor Annotation of

Matrix-Assisted Laser Desorption/Ionization (MALDI) Data

Falk Zakrzewski 1; Linna Sommer 1; Christian Sperling 1; Annelie Zürich 1;

Walter De Back 2; Nico Scherf 2; Ingo Röder 2, 3; Daniela Aust 1, 3;

Pia Hönscheid 1, 3; Gustavo Baretton 1, 3

1Institut für Pathologie des Universitätsklinikums Carl Gustav Carus, Dresden,

Deutschland

2Technische Universität Dresden, Dresden, Deutschland

3Nationales Centrum für Tumorerkrankungen (NCT) Dresden, Dresden,

Deutschland

Purpose: Proteins and peptides represent the phenotype of the tumor at

the time of treatment. Consequently, the tumor proteome is a promising

target to dene novel biomarkers. MALDI combines the identication of

the proteome by means of mass spectra according to time-of-ight masses

(m/z), and the macroscopic anatomy of the tissue compartments. Deep

Learning is largely suitable for addressing the complex MALDI data for

automation of tumor classication by identication of tumor-specic pep-

tide features. erefore, a complementation of MALDI with Deep Learn-

ing pipelines will largely bring forward automated pathological tumor

slide analysis.

Methods: Regions of interest (ROI) of human cancer tissue slides are de-

ned by pathologists and are translated into mass spectra patterns used

for protein/peptide composition and quantication by MALDI. e data

is then transferred into Convolutional Neural Networks (CNNs) for ex-

tracting ROI-specic features. ese trained CNNs are subsequently ap-

plied for autonomous prediction of the tumor content and tumor tissue

localization in previously uncharacterized tissue slides from tumor sam-

ples on the basis of their MALDI spectra.

Results: Trained CNNs can be used to automatically classify, quantify

and mark tumor regions in MALDI imaging data. Morphologically in-

distinguishable tumors can be subdivided and analyzed regarding their

molecule-dependent heterogeneity at a very high resolution (down to 5x5

micrometer).

Conclusions: Our mission is to oer MALDI imaging as a diagnostic

complement for immunohistochemically analysis. We will provide our

MALDI pipeline as a broad application in CNN-based automated tumor

diagnostics and cancer research projects to enable the identication of

new protein/peptide biomarkers.

Leukemia, Myelodysplasia, Transplantation

Best-of-Abstracts-Vorträge

420

Nilotinib (NIL) vs. NIL Plus Pegylated Interferon alpha2B (IFN)

Induction and NIL or IFN Maintenance Therapy for Newly

Diagnosed BCR-ABL1+ Chronic Myeloid Leukemia (CML)

Patients (PTS) in Chronic Phase

Thomas Ernst 1; Susanne Saußele 2; Andreas Burchert 3;

Gabriela Maria Baerlocher 4; Tim Henrik Brümmendorf 5;

Paul Graf La Rosée 6; Dominik Heim 7; Stefan W Krause 8;

Philipp Le Coutre 9; Dietger Niederwieser 10; Thoralf Lange 11;

Mathias Hänel 12; Frank Stegelmann 13; Kirsi Manz 14;

Danny Himsel 1; Rüdiger Hehlmann 15; Christian Fabisch 1;

Markus Prrmann 14; Andreas Hochhaus 1

1Klinik für Innere Medizin II (Hämatologie/Onkologie), Universitätsklinikum

Jena, Jena, Deutschland

2Universitätsmedizin Mannheim

3Philipps Universität Marburg

4Inselspital Bern

5Uniklinik RWTH Aachen

6Schwarzwald-Baar Klinikum, Villingen-Schwenningen

7University Hospital Basel

8Universitätsklinikum Erlangen

9Charité - Universitätsmedizin Berlin

10University of Leipzig

11Asklepios Klinikum Weissenfels

12Klinikum Chemnitz

13University Hospital of Ulm

14IBE Ludwig-Maximilians-Universität München

15ELN-Foundation

Purpose: e TIGER-study (NCT01657604) is a multicenter, randomized

phase III trial to evaluate ecacy an d to lerability of NIL 2*300mg/d

monotherapy vs NIL 2*300mg/d + IFN and the option to discontinue

therapy aer IFN maintenance as  rst line th erapy fo r ch ronic ph ase

CML pts.

Methods: 717 pts (429 male; median age 50.3 yrs, range 18-85) were re-

cruited from 109 sites in Germany, Switzerland, and the Czech Republic.

692 pts were randomized to receive NIL monotherapy (n=353) or NIL/

IFN combination therapy (n=339). Median observation time was 41 mo.

477 pts concluded the induction phase (conrmed major molecular re-

sponse, MMR, BCR-ABL1 <0.1% IS, aer >2 yrs of therapy) and reached

the maintenance phase of the study (NIL vs IFN monotherapy). 199 pts

achieved and maintained MR4 (BCR-ABL1 <0.01% IS) for at least one year

and discontinued all therapy.

Results: IFN signicantly improved rates of MR4 and MR4.5 (BCR-ABL1

<0.0032% IS). Median time to MMR was 5.4 vs 5.7 mo, to MR4 12.5 vs

20.9 mo and to MR4.5 23.2 vs 33.8 mo for NIL vs NIL/IFN, respectively.

From 199 pts who discontinued all therapy (MR4 for at least one year) 63

showed a molecular relapse (BCR-ABL1 >0.1%). Relapse free survival by

18 mo aer treatment discontinuation was 61% in the total cohort. 15 pts

(2.1%) progressed to advanced disease; 22 pts (3.1%) received allogeneic

stem cell transplantations.

Conclusions: is per protocol interim analysis demonstrates feasibili-

ty of 1st-line treatment with NIL combined with IFN. High rates of early

molecular responses indicate an option of treatment-free remission. e

addition of IFN to NIL signicantly improved rates of deep molecular re-

sponse (MR4 and MR4.5) at 12 and 18 mo of therapy.

Disclosure Statement: none

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Poster

111

Selective Dependency of MLL-Rearranged Leukemia

on Immunoproteasome Function

Jonas Tönsing 1; Nuria Tubío Santamaría 1, 2; Tina Schnöder 1, 2;

Ulrike Seifert 3; Clemens Cammann 3; Juliane Mohr 1, 4;

Aniruddha Deshpande 5; Joanna Kirkpatrick 2; Alessandro Ori 2;

Florian Perner 6; Florian Heidel 1, 2

1Klinik für Innere Medizin II - Hämatologie und Internistische Onkologie, Jena,

Deutschland

2Leibniz-Institut für Alternsforschung - Fritz-Lipmann- Institut e.V., Jena,

Deutschland

3Friedrich Loeer Institut für Medizinische Mikrobiologie, Greifswald,

Deutschland

4Universitätsklinikum Magdeburg, Institut für Molekulare und Klinische

Immunologie, Magdeburg, Deutschland

5Sanford Burnham Prebys Medical Discovery Institute, Tumor Initiation and

Maintenance Program, National Cancer Institute-Designated Cancer Center,

San Diego, United States

6Dana-Farber Cancer Institute, Department of Pediatric Oncology, Boston,

United States

Purpose: Several pathways control the balance between self-renewal and

dierentiation to maintain leukemia stem cell (LSC) function. To iden-

tify dependencies of oncogenic fusion proteins, we performed global

proteome proling using MLL-AF9 (MA9) or AML1-ETO9a (AE) mu-

rine cells. In MLL-rearranged (MLLr) cells, GSEA revealed enrichment

of pathways related to proteasome function. is enrichment is present

in MLLr-leukemia but not in AE-LSCs. at may indicate an oncogene

specic vulnerability. In published AML datasets, immunoproteasome

(IP) subunits showed higher expression in MLLr compared to non-MLLr-

AML. IP is a proteasome variant constitutively expressed in hematopoietic

cells. It is relevant for mediating stress-responses during inammation.

Methods: To assess for functional dependency of MLLr cells on IP sub-

units we performed a CRISPR/Cas9 dropout screen in MLLr MOLM13

cells. Inactivation of LMP7 (IP subunit) resulted in outcompetition with

3/5 sgRNAs. Specicity of this nding was conrmed in 5 dierent cell

lines by RNAi using 2 shRNAs against LMP7. To conrm these ndings in

primary cells, we used a previously published conventional LMP7 knock-

out mouse model.

Results: LSK cells of LMP7 ko and wildtype mice were retrovirally in-

fected with either MA9 or NUP98-HOXA9 (non-MLLr control) to as-

sess for disease development by serial plating in methylcellulose. Only in

MA9 cells LMP7-deciency limited re-plating capacity. When we injected

MA9-infected LSK cells into recipient mice, recipients of MA9-LMP7-/-

cells and MA9-LMP7+/+ showed development of AML. However, recip-

ients of MA9-LMP7-/- cells had a signicant delay in AML development.

Conclusions: Taken together, our studies uncover a selective dependency

of MLLr-leukemia on IP function and identify LMP7 as a tractable target.

References:

1. Ebstein et al., “Emerging roles of immunoproteasomes beyond MHC class I

antigen processing”, Cell Stem Cell, 2012.

2. García-Prat et al., “Proteostatic and Metabolic Control of Stemness”, Cell Stem

Cell, 2017.

Disclosure Statement: Nothing to disclose.

214

Cytoreductive Treatment in ‘Real Life’ – Analysis of 434

Polycythemia Vera Patients in Germany

Carl Crodel 1; Kathleen Jentsch-Ullrich 2; Lutz Jacobasch 3; Philipp Kiewe 4;

Jens Kisro 5; Jörg Lipke 6; Siegfried Prenninger 7; Marcel Reiser 8;

Regine Wunschel 9; Andreas Hochhaus 1; Florian Heidel 1

1Jena, Klinik für Hämatologie und Onkologie, Universitätsklinikum Jena, Jena,

Deutschland

2Magdeburg, Gemeinschaftspraxis Hämatologie und Onkologie, Magdeburg,

Deutschland

3Dresden, Gemeinschaftspraxis Hämatologie und Onkologie, Dresden,

Deutschland

4Berlin, Onkologischer Schwerpunkt am Oskar-Helene-Heim, Berlin,

Deutschland

5Lübeck, Lübecker Onkologische Schwerpunktpraxis, Lübeck, Deutschland

6Dortmund, Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund,

Deutschland

7Passau, Onkologische Praxis, Passau, Deutschland

8Köln, Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland

9Nürnberg, Novartis Inc., Nürnberg, Deutschland

Purpose: e aim is to evaluate the use of phlebotomy and cytoreductive

therapy in patients with polycythemia vera.

Methods: For this analysis 11 centers provided data on 434 patients - 211

(48.6%) male and 223 (51.4%) female.

Results: Most patients were of older age (mean 71.4 years; 62.7 years at

diagnosis and 63,4% over 60 years).

100 patients (23.0%) had thromboembolic complications at time of diag-

nosis and 61 (14.1%) during treatment. Cardiovascular (CV) risk-factors

were reported for 320 patients (73.7%). Hypertension (86.9%) was the

most prevalent CV risk factor, followed by hypercholesteremia (18.8%),

diabetes mellitus (16.2%) and smoking (15.9%).

Phlebotomy was primary therapy in 301 patients (69.4%). Triggers to

start pharmacologic cytoreduction included the presence of high-risk

criteria (53.2%) and insucient disease control (22.6%). Asymptomatic

iron deciency (5.6%), symptomatic iron deciency (9.3%) and intoler-

ance to phlebotomy (5.3%) contributed to the limitation of phlebotomy

treatment.

Cytoreductive agents included hydroxycarbamide (n=320; 73.3%),

JAK-inhibitors (n=80; 18.4%), Interferon alpha (n=15; 3,5%), IMIDEs

(n=2; 0.5%) and other cytoreductive agents (n=6; 1.4%). While 11 patients

(2.5%) required combination, 137 (31.3%) patients had a persistent need

for phlebotomy.

Conclusions: Age was main factor for the majority of patients being cat-

egorized as ‘high risk’. Although the majority of patients (>60%) present-

ed as ‘high risk’ according to international guidelines, 69.4% of patients

received phlebotomy as primary therapeutic approach. e low number

of primary cytoreductive treatment and occurrence of symptomatic iron

deciency and of intolerance indicates the need to reconsider indication

and limitations of phlebotomy.

Phlebotomy as a prophylactic measure of risk reduction should result in

mild iron-decient erythropoiesis and hematocrit control. Pharmacologic

cytoreduction is necessary for high risk patients older than 60 years or

with previous thromboembolic complications.

Disclosure Statement:

Regine Wunschel-Nürnberg;Novartis Inc.; Nürnberg; Deutschland

- Beschäigungsverhältnis als Mitarbeiterin bei Novartis

Andreas Hochhaus-Jena;Klinik für Hämatologie und Onkologie; Universitätsk-

linikum Jena; Jena; Deutschland

- Kongresspräsident

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486

Prevalence and Dynamics of BCR-ABL Independent Gene

Mutations in Chronic Phase CML Patients

Lioba Ruppert 1; Jenny Rinke 1; Anja Waldau 1; Markus Prrmann 2;

Andreas Hochhaus 1; Thomas Ernst 1

1Klinik für Innere Medizin II, Onkologisches Forschungslabor,

Universitätsklinikum Jena, Jena, Deutschland

2Institut für medizinische Informationsverarbeitung, Biometrie und

Epidemiologie, Ludwig-Maximilians-Universität München, München,

Deutschland

Purpose: Living without treatment has become a realistic aim for patients

with chronic myeloid leukemia (CML) who achieved durable deep mo-

lecular remission under treatment with tyrosine kinase inhibitors (TKI).

Recently, we have identied novel BCR-ABL independent gene mutations

in newly diagnosed CML patients whereby mutations in epigenetic mod-

ier genes were most common. e prevalence, kinetics and prognostic

signicance of such mutations need to be investigated in a well-charac-

terized patient cohort.

Methods: 100 chronic phase CML patients from the German CML-V (TI-

GER) trial were investigated by targeted deep next-generation sequencing

covering 54 genes frequently mutated in myeloid malignancies. Paired

samples at diagnosis, 12 months, 24 months and 36 months of therapy

were investigated.

Results: Forty-six dierent mutations were detected in 39/100 patients

aecting the genes ASXL1, BCOR, CALR, CUX1, DNMT3A, FBXW7,

IKZF1, JAK2, KDM6A, NOTCH1, RUNX1, STAG2, TET2, TP53, U2AF1

and WT1. ASXL1 (n=13) and DNMT3A (n=9) were most commonly

aected. Nine patients carried more than one mutation. For 26/100 pa-

tients at least one mutation was present at diagnosis. Follow-up samples

revealed that in 22 patients mutations disappeared during TKI treatment.

In 3 patients the mutation persisted indicating that the mutation preced-

ed the BCR-ABL translocation. In 2/97 patients the initial mutation re-

emerged at month 24 aer disappearance at month 12. In 6/100 patients

a new mutation occurred at month 12; 4 of which persisted in further

follow-up samples. Seven mutations were initially detected at month 24

with 2 persisting, and ve mutations at month 36.

Conclusions: BCR-ABL independent gene mutations were frequently

identied in chronic phase CML patients at diagnosis. In a minority of

patients such mutations seem to precede the BCR-ABL translocation in-

dicating a multistep pathogenesis of CML. BCR-ABL independent gene

mutations were found to vary in their dynamics during TKI treatment

and may function as important cofactors in the evolution and persistence

of the disease.

529

Outcome of Refractory and Relapsed Patients with Acute

Myeloid Leukemia

Dietger Niederwieser 1, 1; Rainer Krahl 1; Christoph Kahl 2; Sebastian Scholl 3;

Hans-Heinrich Wolf 4; Michael Cross 1, 5; Ute Hegenbart 6; Norma Peter 7;

Christian Niederwieser 8; Axel Florschütz 9; Kolja F. B. Reifenrath 10;

Niklas Zojer 11; Christian Junghanß 12; Herbert Sayer 13; Volker Schmidt 13;

Georg Maschmeyer 14; Andreas Hochhaus 3; Thomas Fischer 15;

Haifa Kathrin Al-Ali 16; Thomas Heinicke 15

1Universität Leipzig, Leipzig, Deutschland

2Klinikum Magdeburg, Magdeburg, Deutschland

3University Hospital, Jena, Deutschland

4Norbert Kochstr., Nordhausen, Deutschland

5Medical Clinic and Policlinic I, Hematology and Cellular Therapy, Leipzig,

Deutschland

6Universitätsklinikum Heidelberg, Heidelberg, Deutschland

7Department of Internal Medicine, Carl Thieme Klinikum Cottbus, Cottbus,

Deutschland

8Universitätsklinikum , Hamburg Eppendorf, Hamburg, Deutschland

9Klinikum Dessau, Dessau, Deutschland

10Klinikum Oberlausitzer Bergland GmbH, Zittau, Deutschland

11Wien, Österreich

12Klinik für Innere Medizin, Rostock, Deutschland

13Helios Klinikum, Erfurt, Deutschland

14Klinikum Ernst von Bergmann, Potsdam, Deutschland

15Uniklinikum Magdeburg, Magdeburg, Deutschland

16Uniklinikum Halle, Halle, Deutschland

Purpose: Outcome of patients (pts) with refractory Aml or following re-

lapse is usually reported as refractory/relapsed and considered dismal.

Methods: A total of 1621 pts from the OSHO AML 2002 ≤60 y (n=740)

and AML 2004 >60 y (n=881) with newly diagnosed AML (except APL)

eligible for chemotherapy were analyzed. Pts with partial remission (PR)

or non-response (NR) to two induction cycles were considered refractory.

Pts achieving CR and relapsing thereaer were considered relapses and

treated with MitoFlag or Flag-Ida.

Results: A total of 238 (14.7%) pts were refractory (PR 60.1%, NR 39.9%).

OS of refractory pts was 11.4 (7.9-16.6)% @5y, and dependent upon PR

[13.1 (8.1-21.1) % @10y] and NR [5.2 (2.1-12.6)% @5y; p=0.0003]. In-

tensive chemotherapy ± HSCT and hypomethylating agents (HMA)

were able to induce CR in 24.8%. CR pts had an OS of 42.7 (31.4-58.2)

% @5y. Risk factors for OS in refractory pts were age and type of therapy

(p<0.0001). Younger patients with FLT3 mut had a trend for inferior OS

(p=0.1). Almost all long term survivors were treated with HSCT.

Of the 1144 CR/CRi pts, 582 relapsed 1-121 months (mts) aer CR. Age,

cytogenetic risk, type of AML, interval CR to relapse and HSCT were the

dominant factors for relapse. A total of 198 pts received palliative treat-

ment. CR2 was achieved aer intensive chemotherapy ± HSCT, ± DLI

and HMA in 227 pts (39.0%). OS of relapsed pts was 13.8 (11.1 – 17.3) %

@5y. Pts with CR2 had a LFS of 24.9 (19.5-31.7) % @5y and was highest

in patients when intensive chemotherapy followed by HSCT was involved.

Conclusions: Outcome of pts with refractory and relapsed AML is consis-

tent >10% @5y. Age, proportion of palliative treatment and in younger pts

FLT3 mut was recognized as a determinant for OS. However, refractory

and relapsed pts have dierent outcomes and results depend upon PR, NR

and CR. Increase of CR rate in younger but especially in elderly pts with

second generation TKI, reduction of TRM using FLT3-inhibitor mono-

therapy and the option to treat pts ineligible to chemotherapy promise

better outcome.

Disclosure Statement: Cellectis and Daichii

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554

Unfavorable Prognosis of Patients with Acute Myeloid

Leukemia and Central Nervous System Involvement

Sebastian Birndt; Maximilian Fleischmann; Tobias Rachow;

Inken Hilgendorf; Sebastian Scholl; Andreas Hochhaus; Ulf Schnetzke

Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland

Purpose: Central nervous system (CNS) involvement in acute myeloid

leukemia (AML) is rare and associated with a poor outcome. Systematic

data is scarce and cerebrospinal uid puncture (CFP) is not recommended

in current guidelines at any time point of the disease. However, distinct

signs and symptoms should raise awareness of CNS involvement in AML

patients (pts).

Methods: In this retrospective single center analysis, we analyzed 18 AML

pts identied by screening our in-house database using the keywords

“meningeosis” and “AML” diagnosed between 2006 and 2019. All pts re-

ceived CFP and blasts were detected in all samples by microscopy and/or

ow cytometry. Further characterization was performed by clinical, mo-

lecular and pathological parameters.

Results: 18 pts (6 female/ 12 male) with a median age of 55 years at diag-

nosis (range, 27-77) were identied. Clinical symptoms were headache,

lack of vigilance, nausea or distinct neurological symptoms like cranial

or peripheral nerve palsies. Besides meningeal involvement, 5 pts (28 %)

also had solid CNS manifestations. 6 pts (33 %) presented with CNS in-

volvement at initial diagnosis, 12 (66 %) at relapse. 9 pts (50 %) under-

went allogeneic stem cell transplantation (SCT), 6 (33 %) had meningeal

relapse aer allogeneic SCT and 3 pts (17%) showed CNS involvement

before allogeneic SCT. Only 2 pts (11 %) are still alive, both of them had

CNS involvement before allogeneic SCT. Median survival aer diagnosis

of CNS involvement was 205 days (range, 2-3475). 16 of 18 pts (88 %)

received intrathecal chemotherapy; in individual cases radiation was ap-

plied. e majority of pts were categorized into adverse and intermediate

risk group according to current ELN guidelines (7 (38%) and 9 pts (50%),

respectively).

Conclusions: ere is an unmet need for a more vigorous screening for

risk factors of CNS involvement in AML pts due to its poor prognosis.

Several risk factors have been identied that might be associated with the

occurrence of CNS involvement in AML pts. Intensied treatment strate-

gies might be benecial to improve outcome in this patient cohort.

702

Novel Circulating Tumor Dna (CTDNA) Based Ddpcr Drop-

OFF Assays for Improved Minimal Residual Disease (MRD)

Monitoring in Acute Myeloid Leukemia (AML)

Christian Rausch 1; Frank Ziemann 1; Stephanie Schneider 1, 2;

Marion Subklewe 1; Karsten Spiekermann 1; Maja Rothenberg Thurley 1;

Klaus Metzeler 1

1Medizinische Klinik und Poliklinik III, Klinikum der Universität München,

Laboratory for Leukemia Diagnostics, Munich, Deutschland

2University Hospital, LMU Munich, Institute of Human Genetics, Munich,

Deutschland

Purpose: MRD assessment is important for early relapse detection in

AML. MRD monitoring by bone marrow (BM) aspiration is more sen-

sitive than analyses of peripheral blood (pB), yet it is invasive. Moreover,

both fail to detect extramedullary disease (EMD). Analyses of ctDNA may

address these limitations.

Methods: Plasma samples were collected in Streck tubes. CtDNA

was isolated using the QIAampCNA Kit and quantied by Agilent

2100 Bioanalyzer High Sensitivity DNA Kit. Mutations in IDH2 and

NPM1 were detected using custom drop-o ddPCR assays (BioRad

QX200). Mutations in IDH1 and DNMT3A were detected using

commercially available ddPCR assays (Biorad). All assays achieved

<0.1% sensitivity. All patients provided written informed consent.

Results: We regularly monitored ctDNA, bulk pB cell and BM gDNA in

13 patients with previously untreated AML during induction therapy with

the following mutations: NPM1 (Type A, n=7; Type V, N=1), DNMT3A

(R882H, n=4), IDH1 (R132H, n=1) and IDH2 (R140Q, n=2; R172K, n=2).

Variant Allele Frequencies (VAF) of BM- and ctDNA-samples correlated

closely. Sensitivity of ctDNA samples was similar to ddPCR analyses of

BM gDNA, and superior to pB cell gDNA. Mutations were detectable in

ctDNA beyond pB blast clearance, and in one case a mutation present

in EMD but not in BM was detected in ctDNA, indicating that ctDNA

noninvasively captures relevant disease compartments. Absolute

ctDNA levels correlated closely to known causes of cell turnover such

as infections or BM regeneration. However, in cases in which both

mutation VAF and absolute ctDNA levels rose, AML progressed.

Conclusions: We are currently investigating the prognostic value of

response kinetics during treatment. Patient recruitment is ongoing, and

updated data will be presented. ddPCR-based ctDNA analysis allows

minimally invasive AML monitoring. ctDNA analyses may be more

sensitive than pB-cell gDNA and may capture EMD.

Disclosure Statement: e authors have no conicts of interest to disclose.

742

MARS: Mutation-Adjusted Risk Score for Advanced Systemic

Mastocytosis

Mohamad Jawhar 1; Juliana Schwaab 1; Iván Álvarez-Twose 2;

Khalid Shoumariyeh 3; Nicole Naumann 1; Johannes Lübke 1;

Cecelia Perkins 4; Javier I Muñoz-González 2; Manja Meggendorfer 5;

Vanessa Kennedy 6; Georgia Metzgeroth 1; Alice Fabarius 1;

Dietmar Pfeifer 3; Karl Sotlar 7; Hans-Peter Horny 8; Nikolas von Bubno 3;

Torsten Haferlach 5; Nicholas C.P. Cross 9; Wolf-Karsten Hofmann 1;

Wolfgang R. Sperr 10; Andrés C García-Montero 2; Peter Valent 10;

Jason Gotlib 6; Alberto Orfao 2; Andreas Reiter 1

1Hematology and Oncology, University Hospital Mannheim, Heidelberg

University, Mannheim, Germany

2Spanish Network on Mastocytosis (REMA), Toledo and Salamanca, Spain

3Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty

of Medicine, University of Freiburg, Freiburg, Germany

4^Division of Hematology, Department of Medicine, Stanford University School

of Medicine/Stanford Cancer Institute, Stanford, United States

5Munich Leukemia Lab (MLL), Munich, Germany

6Division of Hematology, Department of Medicine, Stanford University School

of Medicine/Stanford Cancer Institute, Stanford, United States

7Institute of Pathology, Medical University of Salzburg, Salzburg, Austria

8Institute of Pathology, Ludwig-Maximilians-Universit, Munich, Germany

9Wessex Regional Genetics Laboratory, Salisbury, United Kingdom

10Internal Medicine I, Division of Hematology and Hemostaseology, Ludwig

Boltzmann Institute for Hematology and Oncology, Medical University of

Vienna, Vienna, Austria

Purpose: With the aim to establish a prognostic score for advanced sys-

temic mastocytosis (AdvSM), we evaluated a large cohort of clinically and

genetically well characterized patients who were enrolled within the ‘Ger-

man Registry on Disoders of Eosinophils and Mast Cells’. e proposed

mutation-adjusted risk score (MARS) was subsequently validated in an

independent cohort of AdvSM patients derived from several centers with-

in the European Competence Network on Mastocytosis (ECNM).

Methods: A total of 383 AdvSM patients were included. e diagnosis

of AdvSM was established according to the WHO classication. Molec-

ular analyses were performed at diagnosis. Targeted Next-Generation Se-

quencing (NGS) was performed to investigate mutation status of KIT and

32 myeloid genes.

Results: In multivariable analysis, the following risk factors were iden-

tied as being associated with overall survival (OS): age greater than 60

years, anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelets < 100

< 109/L), presence of one high molecular risk gene mutation (ie, in SRSF2,

ASXL1, and/or RUNX1), and presence of two or more high molecular risk

gene mutations. By assigning hazard ratio–weighted points to these vari-

ables, the following three risk categories were dened: low risk (median

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OS, not reached), intermediate risk (median OS, 3.9 years; 95% CI, 2.1 to

5.7 years), and high risk (median OS, 1.9 years; 95% CI, 1.3 to 2.6 years;

P < .001). e MARS was independent of the WHO classication and

was conrmed in the independent validation set. During a median fol-

low-up time of 2.2 years (range, 0 to 23 years), 63 (16%) of 383 patients

experienced a leukemic transformation to secondary mast cell leukemia

(32%) or secondary acute myeloid leukemia (68%). e MARS was also

predictive for leukemia-free survival (P < .001).

Conclusions: e MARS is a validated, ve-parameter, WHO-indepen-

dent prognostic score that denes three risk groups among patients with

AdvSM and may improve up-front treatment stratication for these rare

hematologic neoplasms.

Disclosure Statement: nothing to disclose

744

Accurate and Reproducible Measurement of BCR-ABL1 (IS)

Using Digital PCR: Results from a EUTOS Ring Trial

Georg-Nikolaus Franke 1; Niels Pallisgaard 2; Jacqueline Maier 1;

Kathrin Wildenberger 1; Katerina Machova Polakova 3; Matthew Salmon 4;

Nicholas C. P. Cross 4; Helen E. White 4; Guiseppe Saglio 5; Enrico Gottardi 5;

Simona Soverini 6; Andreas Hochhaus 7; Dietger Niederwieser 8;

Thoralf Lange 8, 9; Thomas Ernst 7

1Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Leipzig,

Deutschland

2Zealand University Hospital, Roskilde, Dänemark

3Institute of Hematology and Blood Transfusion, Department of Molecular

Genetics, Prague, Tschechien

4Wessex Regional Genetics Laboratory, Salisbury, United Kingdom

5University of Turin, Department of Clinical and Biological Sciences, Medicine

and Molecular Oncology Laboratories, Turin, Italien

6Bologna University, Department of Experimental, Diagnostic and Specialty

Medicine, Bologna, Italien

7Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland

8Universität Leipzig, Medizinische Fakultät, Leipzig, Deutschland

9Asklepios Klinikum Weißenfels, Klinik für Hämatologie, internistische Onkologie

und Gastroenterologie, Weißenfels, Deutschland

Purpose: BCR-ABL1 positive chronic myeloid leukemia is monitored by

quantitative PCR (RTqPCR). To compare results between dierent labora-

tories alignment to the International Scale (IS) using a conversion factor

(CF) is required, involving a cumbersome process of sample exchange or

lyophilized cell reference material (the LYO-panel)1. We evaluated digital

PCR (dPCR) for monitoring BCR-ABL with regards to interlaboratory

variation, ability to detect deep molecular responses and the CF within the

European Treatment and Outcome Study for CML (EUTOS) consortium.

Methods: Assays for BCR-ABL1 and the reference genes (RG) ABL1 (pro-

vided by Bio-Rad) and BCR (provided by NP) were shipped to 7 laborato-

ries together with the LYO Panel. Samples were prepared and measured in

quadruplicate on two days using local RNA extraction and reverse tran-

scription and the provided assays. Valid results were returned from 6 labs

for central analysis.

Results: Mean %BCR-ABL1/ABL1 for MR1 to MR4.5. was 14.99% (range,

12.23 – 16.95%), 1.36% (0.97 – 1.68%), 0.109% (0.080 – 0.139%), 0.0128%

(0.0105 – 0.0143%) and 0.0081% (0.0022 – 0.0182%), respectively, and

17.11% (14.09 – 23.46%), 1.25% (1.08 – 1.42%), 0.111% (0.090 – 0.135%),

0.0095% (0.0080 – 0.0120%) and 0.0064% (0.0032 – 0.0089%) for BCR-

ABL1/BCR, respectively. %CV for ABL1 and BCR as RG, ranged from

11.3 for MR1 (%BCR-ABL/RG< 10%) to 78.9 for MR4.5 samples. CF to

IS could be calculated for 4/6 labs for BCR and was 0.954 (mean, range

0.868 – 1.097), compared to only 2/6 labs for ABL1 with a mean CF of

1.023 (range 0.851-1.204). e main reason for not being able to calculate

a CF was non-linearity at MR4.5.

Conclusion: Digital PCR reliably detects deep molecular responses. Inter-

laboratory variation was low and the calculated CFs for individual labs lay

within a very narrow band, suggesting that digital PCR might overcome

the need for a lab specic CF. is needs to be tested in a larger trial using

optimized PCR settings for both assays.

Reference:

1. Cross NCP et al. Leukemia 2016

Disclosure Statement: e authors have nothing to disclose.

747

Prognostic Signicance of BAALC and MN1 Expression Levels

During Disease Course in Acute Myeloid Leukemia (AML)

Patients Receiving Allogeneic Stem Cell Transplantation

(HSCT)

Madlen Jentzsch; Marius Bill; Juliane Grimm; Julia Schulz;

Karoline Goldmann; Dominic Brauer; Dietger Niederwieser;

Uwe Platzbecker; Sebastian Schwind

Hämatologie, Zelltherapie, Internistische Onkologie und Hämostaseologie,

Universitätsklinikum Leipzig, Leipzig, Deutschland

Purpose: High pre-treatment expression of the AML-associated genes

BAALC (brain and acute leukemia, cytoplasmic) & MN1 (meningioma-1)

links to adverse outcomes in patients (pts) receiving chemotherapy. e

prognostic signicance in pts receiving allogeneic HSCT for consolida-

tion remains to be elucidated.

Methods: We analyzed 138 AML pts receiving non-myeloablative (3x30

mg/m2 Fludarabine & 2 Gy total body irradiation) allogeneic HSCT (me-

dian age 64, range 32-76 years [y]) in complete remission (CR) or CR with

incomplete recovery (CRi). Digital droplet PCR was applied to quantify

absolute pre-treatment bone marrow BAALC & MN1 copy numbers. For

66 pts, pre-HSCT peripheral blood BAALC & MN1 copy numbers were

assessed in CR/CRi. R’s OptimalCutpoint package dened high & low ex-

pressers, pre-treatment & pre-HSCT respectively. At diagnosis recurrent

mutations by next generation sequencing & ow cytometry patterns were

analyzed. Median follow up was 6.3y.

Results: High pre-treatment BAALC & MN1 copy numbers associated

with a higher CD34 (P<.001 & P<.001, respectively) & CD34+/CD38-

surface antigen expression on mononuclear cells at diagnosis (P<.001 &

P<.001), lower incidence of normal karyotype (P=.008 & P=.04), worse

ELN risk (P=.02 & P=.05), NPM1 wild type (P<.001 & P<.001) & RUNX1

mutations (P=.03 & P=.01). ere was no correlation between pre-treat-

ment & pre-HSCT BAALC (r=.14) or MN1 copy numbers (r=-.06). High

pre-treatment BAALC & MN1 copy numbers associated with higher cu-

mulative incidence of relapse (CIR, P=.05 & P=.05) while overall surviv-

al (OS) was not signicantly dierent (P=.61 & P=.41). In contrast, we

observed a signicantly higher CIR for pts with high pre-HSCT BAALC

(P=.05) or MN1 copy numbers (P=.01) which also translated into shorter

OS (P=.003 & P=.004).

Conclusions: While the adverse prognostic eects of high BAALC & MN1

expression at AML diagnosis might be mitigated aer allogeneic HSCT,

high BAALC or MN1 expression in CR/CRi prior to allogeneic HSCT may

detect residual disease & identify patients at high risk of relapse & shorter

survival.

754

TET2 Mutation Associated Clonal Hematopoiesis is Linked to a

TET2 Polymorphism in Acute Myeloid Leukemia Patients

Dominic Brauer; Juliane Grimm; Madlen Jentzsch; Marius Bill;

Karoline Goldmann; Julia Schulz; Dietger Niederwieser;

Uwe Platzbecker; Sebastian Schwind

University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and

Cellular Therapy, Leipzig, Deutschland

Purpose: TET2 mutations (mut) can be detected in complete remission

(CR), as persistent clonal hematopoiesis (CH), in about 16% of acute my-

eloid leukemia (AML) patients (pts). Several TET2 single nucleotide poly-

morphisms (SNPs) represent missense variants and are linked to altered

gene expression. We analyzed the TET2 coding region for CH associated

SNPs in AML.

Methods: Using a next-generation targeted amplicon sequencing (TAS)

approach we analyzed TET2 exons 3–11 in bone marrow samples at

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diagnosis (dx) in 111 AML pts (median age 64, range 33-75 years) on

the MiSeq platform (Illumina). In a subset of 75 pts in CR or CR with

incomplete recovery (CRi) peripheral blood was tested for CH associat-

ed mut (i.e. in ASXL1, DNMT3A, IDH1, IDH2, IKZF1, JAK2, PPM1D,

SF3B1, SRSF2 & TET2) applying TAS. Mut with variant allele frequency

(VAF) <3% were excluded from further analyses. Outcome analyses were

performed in 102 of these pts; receiving allogeneic hematopoietic stem

cell transplantation (HSCT) in CR/CRi. Median follow up was 6.0 years.

Results: In TET2 SNP rs34402524 (c.5162T>G; p.Leu1721Trp) minor al-

lele (G) presence vs absence associated with TET2 CH mut (26% vs 5%,

P=.02), but not with the presence of CH mut in one of the other analyzed

genes, e.g. in DNMT3A. TET2 SNP rs34402524 allele distribution was

86% T & 14% G. e minor allele SNP frequency in AML was comparable

to healthy caucasians (12% GnomAD; P=.18). e incidence of TET2 mut

at dx did not dier between pts with minor allele (G) presence vs absence

(18% vs 26%, P=.41). e mean VAF of TET2 CH mut did not vary for

pts with minor allele (G) presence vs absence (21% vs 32%, P=.49). Pts

with minor allele (G) undergoing HSCT were by trend less likely to suer

relapse (32% vs 53%, P=.08), but had no dierent overall survival (P=.70).

Conclusions: We found the minor allele (G) in TET2 SNP rs34402524 to

be linked to TET2 mut associated CH in AML pts, but not to the presence

of TET2 mut at dx. Further analyses of a larger set of pts and function-

al studies will improve our understanding of TET2 mut associated CH

in AML.

755

Comparison of Four Dierent Humanized Hematopoietic

Niche Xenotransplantation Models to Engraft Myelodysplastic

Syndromes (MDS)

Eva Altrock 1; Carla Sens-Albert 1; Johann-Christoph Jann 1;

Johanna Flach 1; Vladimir Ryabov 1; Nanni Schmitt 1; Alexander Streuer 1;

Qingyu Xu 1; Verena Nowak 1; Justine Danner 1; Julia Obländer 1; Nina

Draeger 1; Iris Palme 1; Ahmed Jawhar 2; Cleo-Aron Weis 3; Vanessa Weyer 4;

Florian Nolte 1; Georgia Metzgeroth 1; Alexander Marx 3;

Christoph Groden 4; Wolf-Karsten Hofmann 1; Daniel Nowak 1

1Department of Hematology and Oncology, Medical Faculty Mannheim,

Heidelberg University, Mannheim, Deutschland

2Department of Orthopedics and Traumatology, Medical Faculty Mannheim,

Heidelberg University, Mannheim, Deutschland

3Institute of Pathology, Medical Faculty Mannheim, Heidelberg University,

Mannheim, Deutschland

4Department of Neuroradiology, Medical Faculty Mannheim, Heidelberg

University, Mannheim, Deutschland

Purpose: Xenogra models in NSG mice have emerged as versatile

preclinical platforms for investigation of functional pathomechanisms

in MDS ([1] Medyouf et al., 2014, [2] Rouault-Pierre et al., 2017). e

limiting factor of these models is the low engrament of patient-derived

CD34+ hematopoietic stem cells (HSCs). Ecient humanized 3D scaf-

folds in NSG mouse models have been established, enabling to increase

engrament rates of normal and malignant hematopoiesis ([3] Reinisch et

al., 2016current models do not fully mimic the components of the human

bone marrow (BM, [4] Abarrategi et al., 2017). erefore, we evaluated

engrament ability of IPSS low-risk, int-1 and high-risk-patient samples,

in four dierent 3D scaolds.

Methods: We transplanted samples from 10 MDS patients in parallel into

NSG mice testing the following conditions: A) Intrafemoral co-injection

of CD34+ HSCs and MSCs according to [1]. Subcutaneous implantation

of 3D scaolds. Gelfoam (B) and Bio-OSS (C) [4], Matrigel ossicles (D)

[3] and primary human bone isolated aer hip replacement, inserted with

Gelfoam, preseeded in vitro with MSCs and mononuclear cells (MNCs)

and injected in vivo with CD34+ HSCs 8 weeks aer implantation (hu-

man bone ossicles = HBO) (E).

Results: Gelfoam and HBO showed signicantly higher hCD45+cell

numbers compared to intrafemoral injection analyzed by ow cytome-

try. We found systemic engrament of hCD45+cells outside the injected

bone fragment in the BM and spleen solely in mice, which received HBO.

is could possibly be explained due to transplantation of MNCs in this

condition. at was supported by another set of experiments using HBO

(n=10), which showed that colonization of the scaold was similar when

transplanting either CD34+ cells + MSCs, MNCs + MSCs or MNCs only

but systemic engrament could only be seen in MNC transplanted mice.

Conclusions: Our data show that hCD45+cells and MSCs from MDS BM

were able to colonize humanized ossicle scaolds. Gelfoam and HBO were

the most promising novel methods to improve MDS xenogra models.

For systemic engrament, application of MNCs seems to be necessary.

Disclosure Statement: nothing to disclose

781

Treatment with Romiplostim in Patients with Lower-Risk

Myelodysplastic Syndrome (MDS) and Thrombocytopenia -

Results of the Europe Trial By the Emsco Network

Anne Sophie Kubasch 1; Aristoteles Giagounidis 2; Georgia Metzgeroth 3;

Anna Jonasova 4; Regina Herbst 5; José Miguel Torregrosa Diaz 6;

Benoit De Renzis 7; Katharina Götze 8; Marie-Luise Hütter-Krönke 9;

Marie-Pierre Gourin 10; Sophie Dimicoli-Salazar 11;

Pascale Cony-Makhoul 12; Sophie Park 13; Katja Jersemann 14;

Oliver Tiebel 15; Katja Sockel 16; Silke Gloaguen 17; Anna Mies 16;

Fatiha Chermat 18; Christian Thiede 16; Rosa Sapena 18; Richard F Schlenk 19;

Pierre Fenaux 20; Lionel Ades 20; Uwe Platzbecker 1

1Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig

University Hospital, Leipzig, Deutschland

2Department of Oncology, Hematology and Palliative Care, Marien Hospital

Düsseldorf, Düsseldorf, Deutschland

3Department of Hematology and Oncology, University Medical Centre

Mannheim, Mannheim, Deutschland

4Department of Hematology, First Faculty of Medicine, Charles University and

General University Hospital, Prague, Tschechien

5Internal Medicine III, Department of Hematology, Oncology, Stem Cell

Transplantation, Klinikum Chemnitz gGmbH, Chemnitz, Deutschland

6Department of Hematology and Oncology, CHU de Poitiers, Poitiers, Frankreich

7Service d’Hématologie, CHU Clermont‐Ferrand, Clermont‐Ferrand, Frankreich

8Medical Department III for Hematology and Oncology, Klinikum rechts der Isar,

Technische Universität München, München, Deutschland

9Department of Internal Medicine III, University of Ulm, Ulm, Deutschland

10CHRU de Limoges, Limoges, Frankreich

11Department of Hematology, Hôpital Haut Lévèque, University Hospital

Bordeaux, Pessac, Frankreich

12Centre Hospitalier Annecy Genevois, Épagny-Metz-Tessy, Frankreich

13Department of Hematology, CHU Grenoble-Alpes, Grenoble, Frankreich

14GWT-TUD GmbH, Dresden, Deutschland

15Institute of Clinical Chemistry and Laboratory Medicine, University Hospital

Dresden, Technical University of Dresden, Dresden, Deutschland

16Medical Clinic and Policlinic 1, University Hospital Dresden, Dresden,

Deutschland

17The European MDS studies cooperative group (EMSCO), www.emsco.eu

18Groupe Francophone des Myélodysplasies (GFM), Paris, Frankreich

19Department of Internal Medicine V, Heidelberg University Hospital,

Heidelberg, Deutschland

20Hématologie clinique, Hôpital Saint-Louis, Paris, Frankreich

Purpose: e thrombopoietin receptor agonist (TPO-RA) romiplostim

has shown safety and ecacy in a poorly-dened subset of lower-risk (LR)

myelodysplastic syndrome (MDS) patients with thrombocytopenia.

Methods: e EUROPE multicenter phase 2 trial investigated the im-

pact of endogenous thrombopoietin (TPO) level and platelet transfusion

events (PTE) on the ecacy of romiplostim treatment in patients with LR-

MDS (IPSS low/int-1). Patients were eligible if baseline bone marrow blast

count was <5% and platelet counts were ≤30 G/L or ≤50 G/L in case of

bleeding history. Patients were assigned into 3 dierent cohorts at the time

of screening based on their previous PTE and TPO serum levels (cohort

A TPO<500 ng/l, PTE<6U/past year; cohort B: TPO<500 ng/l, PTE≥6U

or TPO≥500 ng/l, PTE<6U, cohort C: TPO≥ 500 ng/l, PTE≥6U). Primary

endpoint of the study was the rate of hematologic improvement of plate-

lets (HI-P) according to IWG 2006 criteria aer 16 weeks of romiplostim

treatment.

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Results: A total of 68 patients with a median platelet count of 25 G/L

(range 1-50 G/L) were included and stratied into cohort A (n=47), B

(n=17) or C (n=4), respectively. Two patients had transient increases in

peripheral blasts to >10% and 1 patient progressed to AML aer 1 month

of treatment. HI-P was observed in 26 of 68 (38%) patients, while re-

sponse was ongoing in 24 of them beyond week 16. Rate of HI-P lasting

for at least 8 weeks was higher in cohort A (45%) compared to patients in

cohort B and C (24%) (p=0.11). Explorative analysis showed a correlation

between pretreatment PTE and endogenous TPO-levels (p=0.034). Eval-

uation of the mutational prole in a subgroup of 49 patients demonstrat-

ed that 67% of responders exhibited spliceosome mutations compared to

35% in non-responders (p=0.06).

Conclusions: e EUROPE study conrms that romiplostim treatment

is eective in a subgroup of LR-MDS patients, neither baseline PTE nor

baseline TPO levels were signicantly associated with response. Further

translational studies are ongoing to elucidate biomarkers of response.

Disclosures: Study funding from Amgen

Lung Cancer

Poster

181

Treatment Patterns of EGFR MT+ NSCLC IV PTS: Real World

Data of the Nowel Network

Julia Roeper 1, 2; Markus Falk 2, 3; Katrin Wedeken 4; Ursula Stropiep 4;

Markus Tiemann 2, 3; Lukas C. Heukamp 2, 3; Claas Wesseler 5;

Sandra Sackmann 6; Frank Griesinger 1, 2

1Universitätsklinik Innere Medizin-Onkologie Carl v. Ossietzky Universität

Oldenburg, Pius Hospital Oldenburg, Oldenburg, Deutschland

2Lung Cancer Network NOWEL.org Oldenburg, Oldenburg, Deutschland

3Institut für Hämatopathologie Hamburg, Hamburg, Deutschland

4Pius Hospital Oldenburg, Oldenburg, Deutschland

5Asklepios Klinikum Harburg, Hamburg, Deutschland

6Klinikum Bremen-Ost, Bremen, Deutschland

Purpose: e percentage of pts switching from 1st gen TKI in 1st line to 3rd

gen TKI in 2nd line seems to be low with 30% and it is questionable wheth-

er these data represent real world treatments1. erefore, we investigated

the treatment pattern and especially the attrition rate between 1st and 2nd

line therapy in EGFR mt+ pts.

Methods: 965/1536 (63%) pts with non-squamous NSCLC IV were test-

ed for EGFR mt+. 148/965 (15%) pts with an EGFR mt+ were identied.

To calculate PFS and OS we used Kaplan Meier and the log rang test for

p-values.

Results: 144/148 pts were treated with TKI on 1st or 2nd line (aer chemo-

therapy). 14/144 pts are still on 1st line, 9 pts were lost to follow-up and

3 pts died while on 1st line. We identied 118/144 candidates for 2nd line

therapy (because of progression on 1st line TKI) and only 84/118 (70%)

pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd

line therapy because of bad PS (n=26), pts refusal (n=2), fast progression

(n=6) and death (n=2). Aer accessibility of 3rd gen TKI 72 pts were candi-

dates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy.

mOS of pts receiving 2nd line therapy aer access to 3rd gen TKI was 35 mo

for pts with 2nd line therapy vs. 10 mo without 2nd line (p<0.000). 32/51

pts (63%) were tested for T790M and 20/32 (62%) were T790M+. Highest

T790M test rate in one center was 22/28 (79%). 16/20 (80%) T790M+ pts

received 3rd gen TKI for 2nd line therapy. mOS of pts receiving 3rd gen TKI

(n=31) was 51 mo vs. 25 mo for pts without 3rd gen TKI (p<0.002).

Conclusions: A signicant number of pts treated with 1st or 2nd gen TKI

do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI.

Reasons for not receiving 2nd line therapy are in most cases deterioration

of PS, death and no testing for T790M in a minority of cases. ese data

are important for the interpretation of the OS data of the FLAURA study1

as they reect real world treatment algorithms in dedicated German lung

cancer centers.

Reference:

1. Soria J-CH et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–

Small-Cell Lung Cancer. N Engl J Med 2018; 378:113-125

Conicts of Interest:

Julia Roeper: Honorarium: Roche, Boehringer Ingelheim

Markus Falk: e authors declare no potential conict of interest.

Ursula Stropiep: e authors declare no potential conict of interest.

Markus Tiemann: Honorarium: Astra Zeneca, Boehringer Ingelheim, Novartis,

Roche, Pzer, Takeda, BMS, MSD

Travel costs: Boehringer Ingelheim, Roche, Takeda, BMS, MSD

Lukas C. Heukamp: Honararium: NEO New Oncology, BMS, Bayer, Roche, Pzer

Advisory board: NEO New Oncology, BMS, Bayer, Roche, Pzer

Class Wessler: e authors declare no potential conict of interest.

Sandra Sackmann: e authors declare no potential conict of interest.

Frank Griesinger: Honorarium: Astra Zeneca, Boehringer Ingelheim, BMS,

Celgene, Lilly, MSD, Novartis, Pzer, Roche, Takeda, Ariad, Abbvie, Siemens

Advisory board: ASTRA, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pzer,

Roche, Takeda, Ariad, Abbvie, Siemens

Research fund: Astra Zeneca, Boehringer, BMS, Celgene, Lilly, MSD, Novartis,

Pzer, Roche, Takeda, Siemens

190

Sophisticated Epitope Quality-Based Approach Reveals

Patient’s Suitability for Immune Checkpoint Inhibition

Michael Wessolly 1, 2; Susann Stephan-Falkenau 3; Anna Streubel 3;

Robert Werner 3; Sabrina Borchert 1, 2; Sergej Gri 4; Elena Mairinger 1;

Robert Walter 1, 5; Torsten Bauer 4; Wilfried Eberhardt 5, 6;

Torsten Gerriet Blum 4; Kurt Werner Schmid 1; Jens Kollmeier 4;

Thomas Mairinger 3; Fabian Dominik Mairinger 1, 2

1Universitätsklinikum, Institut für Pathologie, Essen, Deutschland

2German Cancer Consortium (DKTK), Partner Site University Hospital Essen,

Essen, Deutschland

3Helios Klinikum Emil von Behring, Fachbereich Gewebsdiagnostik/Pathologie,

Berlin, Deutschland

4Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn, Berlin,

Deutschland

5Ruhrlandklinik, Westdeutsches Lungenzentrum, Essen, Deutschland

6Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Essen,

Deutschland

Purpose: Immune checkpoint inhibition, especially the blockade of PD-1

and PD-L1, has developed into one of the most prosperous therapeutic

approaches in modern oncology. Despite promising clinical results, re-

sistance acquirement remains a perpetual problem1. One possible escape

mechanism, which mediates therapy failure might be linked altered epi-

tope processing (processing escapes)2. In the present study, we aim to

demonstrate the eects of processing escapes on immunotherapy out-

come in NSCLC-patients.

Methods: e cohort was comprised of primary tumor samples from

48 NSCLC-patients. Everyone received Nivolumab at one point of

their treatment. Mutations were identied by targeted amplicon-

based sequencing including hotspots and whole exomes of 22 genes.

Convolutional neural networks were utilized to examine the eect of

mutations on proteasomal processing. e algorithm was previously

trained on 1260 known MHC-I ligands. Possible inuences on Overall

survival were calculated by Cox-regression.

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Results: In the validation cohort, patients displaying both processing

escapes and high expression rates PD-L1 (n=8/48) showed signicantly

shortened overall survival, independent of mutational load or PD-L1 sta-

tus alone in multivariate analysis.

Conclusions: e concept of altered epitope processing might broaden

our horizon in understanding immune therapy failure. Especially when

combined with PD-L1 status, this method could provide important neg-

ative predictive value, potentially becoming a foundation in the I/O ther-

apy decision process.

References:

1. Wessolly M, Mairinger F. Processing Escapes: A New Perspective on Im-

mune Escape Mechanisms. Canc erapy & Oncol Int J. 2017;5(3):CTOIJ.

MS.ID.555662.

2. Wessolly M, Walter RFH, Vollbrecht C, et al. Processing Escape Mecha-

nisms rough Altered Proteasomal Cleavage of Epitopes Aect Immune

Response in Pulmonary Neuroendocrine Tumors. Technol Cancer Res Treat.

2018;17:1533033818818418.

Disclosure Statement: All authors formally declare that there are no conicts of

interest

201

Long Time Remission in NSCLC Stage iv After Stopping

Immunotherapy Due to Severe Side Eects - a Report

of Two Cases

Helge G. Bischo 1; Christiane Wiedemann 1; Maria Sianidou 2;

Petros Christopoulos 2; Claus Peter Heußel 2; Michael Thomas 2

1Thoraxklinik, Heidelberg, Deutschland

2Thoraxklinik, Radiologie, Heidelberg, Deutschland

Purpose: Immunotherapy is an important element in the treatment of

NSCLC. Side eects of immunotherapy due to autoimmune reactions can

lead to severe problems.

Methods: We report two cases with long time remission aer stop of Im-

munotherapy due to side eects

Results:

Case 1: A 62 y old male was diagnosed with NSCLC; adeno cancer stage

IV in September 2017. No targetable mutations were found, PDL1 was

50%. An Immunotherapy with Pembrolizumab was initiated in October.

CT scan in December 2017 demonstrated PR. Brain metastases were ir-

ridiated in November and December 2017. In December, the patient de-

veloped interstitial pneumonia WHO grade 3 and was treated with high

dose corticosteroids. e immunotherapy was therefore terminated aer

2 cycles in 2017. e patient shows still stable disease without progression

until August 2019.

Case 2: A 61 y old male was diagnosed with NSCLC; adeno cancer stage

IV in January 2017. No targetable mutations were found, PDL1 was 60%.

An immunotherapy with Pembrolizumab was initiated in February 2017.

e CT Scan showed PR aer 4 cycles in May 2017 and SD aer 12 cycles

in November 2017. In November 2017 the patient developed autoimmune

colitis WHO grade 3 and was treated with high dose corticosteroids.

e immunotherapy was therefore terminated aer those 12 cycles. e

patient shows still stable disease without progression until August 2019.

Conclusions:

When immunotherapy has reached a remission and has to be terminated

due to immunologic complications, the complications have to be treated

with immunosuppressive therapy. Aer the remission of the side eects,

the patients might be followed up without systemic therapy under close

clinical observation. In some cases, SD persists. Further tumor-specic

therapy should be only considered, if PD is documented.

238

Delays and Delaying Factors from Symptoms to Diagnosis

in Lung Cancer

Lisa Pisotska 1, 2; Linda Regber 3; Dieter Wuerein 1, 2; Heide Wagner 2;

Joachim Ficker 1, 2; Wolfgang Brückl 1, 2

1Paracelsus Medizinische Privatuniversität Nürnberg, Paracelsus Medical

University, Nürnberg, Deutschland

2Klinikum Nürnberg Nord, Nordklinikum, Department of Respiratory Medicine,

Lung Cancer Center, Nürnberg, Deutschland

3MediStatis.de, Berlin, Deutschland

Purpose: e majority of lung carcinomas are diagnosed and treated in a

late stage. One reason might be long delays between rst symptoms, diag-

nosis and treatment. is study was conducted to identify delays during

the management of patients with lung cancer to assess possible causes for

these delays and to analyze the impact of delays on survival.

Methods: Patients with recently diagnosed lung cancer were prospectively

included. Delays were calculated as: patient’s delay (rst symptom to rst

general practitioner visit); GP delay (rst GP visit to specialist appoint-

ment); specialist’s delay (specialist appointment to hospital referral); hos-

pital delay (hospital referral to diagnosis) and treatment delay (diagnosis

to therapy initiation). Delays were analyzed in relation to clinical char-

acteristics and factors for delays were assessed by uni- and multivariate

analyses.

Results: 220 patients were included (60.9% male; median age of 63.5

years; 30.3% SCLC, 77.7% ex-smokers). e median patient’s delay, GP

delay, specialist’s delay, hospital delay and treatment delay was 5 days

(mean 20.9), 15 days (mean 38.9), 11 days (mean 27.2), 8 days (mean 14.3)

and 15 days (mean 21.4) respectively. Diagnostic intervals were shorter

for patients with SCLC vs NSCLC (median 10.5 vs 16 days, p=0.004) and

for late-stage vs early-stage cancer (median 6 vs 9 days, p=0.025). Patients

<65 years had longer total delay vs those ≥65 years (median 66 vs 49 days,

p=0.035). Patients with dyspnea, cough or hemoptysis had longer patient’s

delay than those without (median 5 vs 3 days, p=0.020), but a shorter

treatment delay (median 14 vs 19 days, p=0.048). No signicant eect on

survival was observed in this cohort.

Conclusions: ere are varieties of causes leading to delays during the

diagnosis of lung cancer. is study provides some insights, which may

help to reduce waiting times by raising awareness of certain demographics

and symptoms and shortening the referral times to improve the overall

outcome for lung cancer patients.

Disclosure Statement: e authors declare that there is no conict of interest.

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242

Relay: a Multinational, Double-Blind, Randomized Phase 3

Study of Erlotinib (ERL) in Combination with Ramucirumab

(RAM) or Placebo (PL) in Previously Untreated Patients with

Epidermal Growth Factor Receptor Mutation-Positive (EGFRM)

Metastatic Non-Small Cell Lung Cancer (NSCLC)

Kazuhiko Nakagawa 2; Edward Garon 3; Takashi Seto 4; Makoto Nishio 5;

Santiago Ponce Aix 6; Chao-Hua Chiu 7; Keunchil Park 8; Silvia Novello 9;

Ernest Nadal 10; Fumio Imamura 11; Kiyotaka Yoh 12; Jin-Yuan Shih 13;

Kwok Hung Au 14; Denis Moro-Sibilot 15; Sotaro Enatsu 16;

Bente Frimodt-Moller 17; Carla Visseren-Grul 18;

Annamaria H. Zimmermann 19; Martin Reck 1

1Großhansdorf, Lungenclinic, Großhansdorf, Deutschland

2Kindai University Hospital, Department of Medical Oncology, Osakasayama,

Japan

3David Geen School of Medicine, University of California, Los Angeles,

United States

4National Hospital Organization Kyushu Medical Center, Fukuoka, Japan

5Department of Thoracic Medical Oncology, , The Cancer Institute Hospital

of Japanese Foundation for Cancer Research, Tokyo, Japan

6Hospital 12 De Octubre, Madrid, Spanien

7Veterans General Hospital, Taiwan

8Samsung Seoul Hospital, Cancer Hospital, Seoul, Südkorea

9Department of Oncology, University of Turin, Orbassano, Italien

10Institut Català d‘Oncologia - L‘Hospitalet de Llobregat, L‘Hospitalet de

Llobregat, Spanien

11Osaka internatioanl cancer center, Osaka, Japan

12National Cancer Center Hospital East, Kashiwa, Japan

13National Taiwan University Hospital, Taipei, Taiwan

14Queen Elizabeth Hospital, Hong kong, Hong Kong

15University Hospital, Grenoble, Frankreich

16Eli Lilly Japan KK, Kobe, Japan

17Eli Lilly Denmark A / S, Herlev, Dänemark

18Lilly Netherlands, Utrecht, Niederlande

19Eli Lilly and Company Corporate Center, Indianapolis, United States

Purpose: RELAY evaluated ecacy and safety of erlotinib (ERL)+ramu-

cirumab (RAM) or placebo (PL) in 1L epidermal growth factor receptor

mutation-positive (EGFRm) metastatic non-small cell lung cancer (NS-

CLC).

Methods: Eligibility: untreated metastatic NSCLC patients (pts) with

Exon19 deletion (del) or L858R and no CNS metastasis. Randomized

(1:1) pts received ERL (150mg/day) +RAM (10mg/kg q2w) or ERL+PL,

stratied by gender, geographic region (East Asia vs other), EGFRm type

(Ex19del vs L858R) and EGFR testing method. Primary endpoint was

investigator-assessed progression free survival (PFS). Other objectives:

overall response rate (ORR), duration of response (DoR), PFS2, overall

survival (OS), safety and plasma T790M mutation.

Results: 449 pts were randomized. Baseline characteristics were balanced

between treatment arms: Asian 77%, Females 63%, Ex19del 54%. PFS was

signicantly prolonged in the RAM-ERL vs PL-ERL group (medians 19.4

months [mos; 95%CI 15.4, 21.6] vs 12.4 mos [95%CI 11.0, 13.5], strati-

ed hazard ratio [HR] .591; 95%CI .461, .760; p<.0001). ORR was similar

between groups (76.3% [95%CI 70.8, 81.9] vs 74.7% [95%CI 69.0, 80.3]).

DOR was longer for pts responding in the RAM-ERL group (medians,

18.0 mos [95%CI 13.9, 19.8] vs 11.1 mos [95%CI 9.7, 12.3], unstratied

HR .619; 95%CI .477, .805; p=.0003); OS data were immature (82% cen-

soring, medians not reached [NR], HR .832 [.532-1.303]; p=.4209). PFS2

favored RAM-ERL (69% censoring rate, medians NR, HR .690, 95%CI

.490, .972; p=.0325). Grade≥3 treatment-emergent adverse events were

greater with RAM (72%) vs PL (54%), largely driven by hypertension (24

vs 5%, no Grade 4), with 1 treatment related on study death (hemothorax)

in RAM vs 0 PL. EGFR T790M+rates at progression are forthcoming.

Conclusions: RAM+ERL led to superior PFS in 1L EGFRm metastatic

NSCLC. Safety was consistent with the established safety proles of the

individual compounds.

accepted and previously presented at 2019 ASCO-55th Annual Meeting. All rights

reserved.

276

NAB-Paclitaxel Plus Carboplatin As First-Line Therapy for

Patients with Advanced NSCLC in the Real-World Setting:

Safety Results of the Non-Interventional Neptun Study

Tobias Dechow 1; Jorge Riera-Knorrenschild 2; Björn Hackanson 3;

Ludwig Fischer von Weikersthal 4; Marco Chiabudini 5; Barbara Timm 5;

Ralf Michael Zerbes 5; Karin Pottho 5

1Onkologie Hämatologie Ravensburg, Ravensburg, Deutschland

2Universitätsklinikum Gießen und Marburg GmbH, Marburg, Deutschland

3Universitätsklinikum Augsburg, Augsburg, Deutschland

4Gesundheitszentrum St. Marien GmbH, Amberg, Deutschland

5iOMEDICO AG, Freiburg im Breisgau, Deutschland

Purpose: In patients with non-small cell lung cancer (NSCLC), the

combination of nab-paclitaxel plus carboplatin is a standard rst-line

regimen. e favorable ecacy and safety prole of this combination has

been shown in a pivotal phase 3 trial and was conrmed for various patient

subpopulations in the consecutive ABOUND studies. e prospective

non-interventional study NEPTUN was designed to analyze eectiveness,

safety and tolerability of this regimen in the real-world setting in Germany.

Methods: In total, 400 patients with stage IIIB/IV NSCLC scheduled to

receive nab-paclitaxel and carboplatin as rst-line therapy were planned

to be recruited in 100 outpatient centers and hospitals across Germany.

Primary endpoint was the six-month progression-free survival rate. Key

secondary endpoints included further eectiveness parameters, safety and

quality of life (QoL). Descriptive statistics were used to analyze data. e

second interim analysis of the NEPTUN study was scheduled to analyze

eectiveness and safety data as well as QoL. Here, we will focus primarily

on the safety results.

Results: Between 08/2016 and 06/2019 408 patients have been enrolled at

74 active sites. Baseline patient and tumor characteristics including age,

ECOG, co-morbidities, histology, and treatment details including dose

modications and reasons will be presented. Safety and tolerability data

will be analyzed including incidence of (severe) adverse events, adverse

drug reactions and use of supportive care.

Conclusions: e NEPTUN study demonstrates an acceptable safety pro-

le of nab-paclitaxel and carboplatin in patients with advanced NSCLC in

a real-world setting. Toxicity is generally mild and manageable, support-

ing the use of this regimen as a rst-line treatment option.

297

Single-ARM Phase II-STUDY in Patients with Extensive Stage

Small-Cell Lung Cancer (ES-SCLC) with Poor Performance

Status Receiving atezolizumab-Carboplatin-Etoposide (Space;

AIO-TRK-0119)

Jan Stratmann 1; Martin Sebastian 1; Martin Reck 2

1Universitätsklinikum Frankfurt, Medizinische Klinik 2: Hämatologie / Onkologie,

Frankfurt am Main, Deutschland

2LungenClinic Großhansdorf, Großhansdorf, Deutschland

Purpose: Small-cell lung cancer (SCLC) is an aggressive tumor with an

unfavorable prognosis that accounts for approximately 15% of all lung

cancers. Two in three patients (pts) diagnosed with SCLC have metasta-

ses (extensive disease, ED) at primary diagnosis. Platinum-based doublet

chemotherapy has been the palliative standard of care in these pts for over

30 years13.

Addition of the PD-L1-antibody atezolizumab results in a signicant and

meaningful OS benet in patients with ED-SCLC, as shown in the IM-

power133 trial4. e trial excluded pts with low performance status, that

account for approximately one-third of all SCLC pts; therefore, to date no

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data is available regarding safety and ecacy of the triplet combination in

this population.

e SPACE study plans to include 70 pts with low performance status to

provide a reasonable estimate of the primary study endpoint of the 1-year

survival rate; secondary endpoints are response rate, progression-free sur-

vival, safety and quality of life.

Methods: Treatment naive pts with ECOG=2 will receive induction treat-

ment consisting of four 21-day cycles of carboplatin (AUC of 5 mg/mL/

min, IV, d1) and etoposide (cumulative total dose of ≥300 mg/m², IV on

3 consecutive days) with atezolizumab (1200 mg IV, d1), followed by a

maintenance phase during which pts receive atezolizumab (Q3W) until

the occurrence of unacceptable toxicity, disease progression or withdraw-

al of consent or death.

Results: Recruitment not yet started.

References:

1. Griesinger, F, et al. Lungenkarzinom, kleinzellig (SCLC) — Onkopedia.

2. Evans WK, et al. VP-16 and cisplatin as rst-line therapy for small-cell lung

cancer. J Clin Oncol, 1985

3. atcher and Lind, Carboplatin in small cell lung cancer. Semin Oncol. 1990

Feb;17(1 Suppl 2):40-8.

4. Horn L, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage

Small-Cell Lung Cancer. NEJM. 2018;379(23):2220–2229. doi:10.1056/NEJ-

Moa1809064.

Disclosure Statement: SPACE (EudraCT 2019-001707-21) study sponsor is

AIO-Studien-gGmbH; Berlin. e study is nancially supported by F. Hofmann-la

Roche.

301

Neoadjuvant Immune Checkpoint Inhibition in Resectable

Lung Cancer

Thorsten Walles 1; Eva Lücke 2; Christine Ganzert 2; Peter Hass 3;

Michael Kreißl 4; Johannes Haybäck 5; Jens Schreiber 2

1Abteilung Thoraxchirurgie, Universitätsmedizin Magdeburg, Magdeburg

2Klinik für Pneumologie, Universitätsmedizin Magdeburg, Magdeburg

3Klinik für Strahlentherapie, Universitätsmedizin Magdeburg, Magdeburg

4Klinik für Nuklearmedizin, Universitätsmedizin Magdeburg, Magdeburg

5Institut für Pathologie, Universitätsmedizin Magdeburg, Magdeburg

Purpose: Pharmacological inhibition of programmed cell death (PD-1)

protein improves survival in patients with advanced non-small-cell lung

cancer (NSCLC) [1]. e clinical eect of neoadjuvant immune check-

point inhibition (ICI) in patients with resectable or oligometastatic dis-

ease is scarcely explored.

Methods: Retrospective single-center cohort analysis. Tissue biopsies of

NSCLC in advanced stage were tested for PD-L1 expression. In patients

with PD-L1 expression > 50%, ICI were administered before surgery with

surgery planned approximately 4 weeks aer the rst dose. Clinical toler-

ance, radiological and histological tumor response and oncological out-

come were analyzed.

Results: Between 2017 and 2019 four patients (2 male, 2 female; age 56-78

years) received ICI before tumor resection. Tumor histology was adeno

carcinoma in 3 and squamous cell carcinoma in 1 case. All patients had

locally advanced tumors T3 or T4. Mediastinal lymph nodes were positive

in 3 cases. In one patient, a single brain metastasis was present that was

treated by radiotherapy. All patients received at least 2 cycles ICI before

surgery (Pembrolizumab in 3 cases, Atezolizumab in 1 case). ICI therapy

was well tolerated and did not delay surgery. According to RECIST crite-

ria, 3 tumors showed partial remission and 1 patient progressive disease.

All tumors were resected completely. Pathological workup of the surgical

specimen conrmed complete pathologic response (CPR) in 2 and partial

pathologic response (PPR) in 2 cases. Mean follow up is 12 months (1-24).

PPR patients developed either distant metastasis aer 6 months or local

recurrence aer 4 months.

Conclusions: ICI is well tolerated in the neoadjuvant setting for NSCLC

and may induce total tumor remission in selected patients. erapy does

not interfere with surgery and is well tolerated by patients. Prognosis is

very promising in CPR and limited in PPR.

Reference:

1. Forde PM, Cha JE, Smith KN et al. Neoadjuvant PD-1 Blockade in Resectable

Lung Cancer. NEJM 2018; 378: 1976-1986.

Disclosure Statement: e authors declare no conict of interest.

374

Non-Invasive Molecular Proling for Therapy Monitoring

of ALK+ Lung Cancer

Steen Dietz 1, 2; Petros Christopoulos 2, 3; Lisa Gu 1, 2; Volker Endris 4;

Zhao Yuan 5; Simon J. Ogrodnik 1; Tomasz Zemojtel 6; Marc A. Schneider 2, 7;

Anna-Lena Volkmar 4; Michael Meister 2, 7; Thomas Muley 2, 7; Martin Reck 8;

Matthias Schlesner 2, 5; Michael Thomas 2, 3; Albrecht Stenzinger 2, 4, 9;

Holger Sültmann 1, 2

1Division of Cancer Genome Research, German Cancer Research Center (DKFZ),

German Cancer Consortium (DKTK), and National Center for Tumor Diseases

(NCT), Heidelberg, Deutschland

2German Center for Lung Research (DZL), TLRC Heidelberg, Heidelberg,

Deutschland

3Department of Oncology, Thoraxklinik at University Hospital Heidelberg,

Heidelberg, Deutschland

4Institute of Pathology at University Hospital Heidelberg, Heidelberg,

Deutschland

5Bioinformatics and Omics Data Analytics, German Cancer Research Center

(DKFZ), Heidelberg, Deutschland

6Berlin Institute of Health (BIH) Genomics Core Facility, Charité University

Medical Center, Berlin, Deutschland

7Translational Research Unit, Thoraxklinik at University Hospital Heidelberg,

Heidelberg, Deutschland

8Lung Clinic Grosshansdorf, Airway Research Center North, German Center for

Lung Research (DZL), Großhansdorf, Deutschland

9German Cancer Consortium (DKTK), Heidelberg, Deutschland

Purpose: Non-small cell lung cancer (NSCLC) patients with ALK rear-

rangements are routinely treated with tyrosine kinase inhibitors (TKIs),

leading to improved survival. However, clinical courses vary widely as the

tumors inevitably develop resistance. us, early detection and molecular

characterization of treatment failure is important for patient outcome.

Methods: To identify indicators of therapy response and progression,

we performed an analysis of circulating tumor DNA (ctDNA) from

serial plasma samples (n=278) of 73 NSCLC patients with ALK

rearrangements. Using targeted sequencing and shallow whole genome

sequencing (sWGS), we achieved mean unique coverages of >4000x and

0.5x, respectively.

Results: Variable mutation levels were marked in all patients and correlat-

ed with clinical features. For example, mutant ctDNA levels were low in

cases of stable disease, but increased at the time of TKI failure. Targeted

sequencing identied known and novel mutations indicating TKI resis-

tance. We also found mutated TP53 at the time of progression in patients

with initially TP53 wildtype tumors. e progression-free survival of pa-

tients with acquired TP53 mutations was comparable to that of primarily

TP53 mutated and shorter than that of persistently TP53 wildtype cases.

sWGS of ctDNA identied copy number variations, some of which might

contribute to tumor progression. We also measured miRNA abundanc-

es in corresponding serum samples and noted uctuating miRNA levels

during therapy that correlated with the clinical course in several cases.

Conclusions: Our data suggest that liquid biopsies can improve ALK+

NSCLC patient care through early detection of progression and tailored

treatment of resistant tumors. ctDNA and miRNA can indicate the need

to switch treatment and provide information to guide the next-line thera-

py. Detection of acquired TP53 mutations in liquid rebiopsies at the time

of disease progression identies additional high-risk cases and suggests

potential clinical utility of ctDNA monitoring for this disease beyond pro-

ling of ALK resistance mutations.

Conicts of Interest:

SD reports speaker’s honoraria from Roche;

PC reports research funding from Novartis, Roche, AstraZeneca and Takeda as

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well as advisory board and/or lecture fees from Boehringer, Pzer and Chugai;

AV reports speaker’s honoraria from Astra Zeneca;

VE reports advisory board and lecture fees from AstraZeneca and ermoFisher;

MT reports advisory board honoraria from Novartis, Lilly, BMS, MSD, Roche,

Celgene, Takeda, AbbVie, Boehringer, speaker’s honoraria from Lilly, MSD,

Takeda, research funding from AstraZeneca, BMS, Celgene, Novartis, Roche and

travel grants from BMS, MSD, Novartis, Boehringer;

AS reports advisory board honoraria from BMS, Bayer, AstraZeneca, ermoFish-

er, Novartis, Seattle Genomics speaker’s honoraria from BMS, Bayer, Illumina,

AstraZeneca, Novartis, ermoFisher, MSD, Roche, as well as research funding

from Chugai, Bayer and BMS;

HS reports advisory board and speaker’s honoraria from Roche.

393

Patients with Metastatic Non-Small Cell Lung Cancer and

Targetable Molecular Alterations in Germany. Treatment and

First Outcome Data from The Prospective German Registry

Platform Crisp (AIO-TRK-0315)

Frank Griesinger 1; Wilfried E E Eberhardt 2; Arnd Nusch 3; Marcel Reiser 4;

Mark-Oliver Zahn 5; Norbert Marschner 6; Martina Jänicke 7; Annette

Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7; Aysun Karatas 8; Annette Hipper 8;

Wilko Weichert 9; Cornelius F Waller 10; Martin Reck 11;

Petros Christopoulos 12; Martin Sebastian 13; Michael Thomas 12

1Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland

2Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland

3Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland

4PIOH - Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland

5Überörtliche Berufsgemeinschaft MVZ Onkologische Kooperation Harz, Goslar,

Deutschland

6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland

7iOMEDICO Freiburg, Freiburg, Deutschland

8AIO-Studien-gGmbH, Berlin, Deutschland

9Technical University of Munich, Institute of Pathology, München, Deutschland

10Universitätsklinikum Freiburg Innere Medizin I, Freiburg, Deutschland

11LungenClinic, Airway Research Center North (ARCN), German Center for Lung

Research (DZL), Grosshansdorf, Deutschland

12Internistische Onkologie der Thoraxtumoren, Thoraxklinik im

Universitätsklinikum Heidelberg, Translational Lung Research Center

Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),

Heidelberg, Deutschland

13University Hospital Frankfurt, Frankfurt a.M., Deutschland

Purpose: Guidelines for stage IV NSCLC recommend stratied treatment

by biomarker test results. We used CRISP to evaluate treatment and out-

come of patients (pts) with targetable molecular alterations.

Methods: Currently 163 sites in Germany have recruited >4255 pts at start

of 1st-line who will be followed until death or end of project. Data from

2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed.

Progression-free survival (PFS) was determined in pts observed ≥1 year

(recruited <06/2017 (n=906), outcome sample (ous)).

Results: 94%/65% of 1732/472 pts with non-squamous/squamous tu-

mors were tested for any biomarker. In 2018 test rate was 96%/75% and

49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with

approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1

or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Of pts

with druggable EGFR mutation (EGFR+ pts, n=149) 78% received EG-

FR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something

else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of

EGFR+ pts was 7.1 months (n = 67, 61% events, 95%-CI 5.2-10.1), in total

46% (n=31) of pts had died (ous). Of pts with druggable ALK alteration

(n=55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-

aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-

line. In the ous (n=29), 55% (n=16) of tumors had already progressed, in

total 24% (n=7) of pts had died. All 6 pts with druggable ROS1 alteration

received chemotherapy, while 6 of the 9 pts with druggable BRAF muta-

tion and start of treatment in 2017/18 received a BRAF-ATT in 1st-line.

Conclusions: Pts are frequently tested for molecular alterations. While

EGFR-aTT is well established as 1st-line and rst data are promising for

BRAF-aTT, pts with ALK/ROS alteration are not routinely treated with

1st-line aTT, reasons are not yet clear.

Disclosure Statement: None of the authors has declared a conict of interest

regarding the subject of this work.

394

Patients with Metastatic Non-Small Cell Lung Cancer and

PD-L1 Expression in Germany. Treatment and First Outcome

from the Prospective German Registry Platform Crisp

(AIO-TRK-0315)

Martin Sebastian 1; Wilfried E E Eberhardt 2; Christoph Losem 3;

Christiane Bernhardt 4; Christoph Maintz 5; Norbert Marschner 6;

Martina Jänicke 7; Annette Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7;

Aysun Karatas 8; Annette Hipper 8; Wilko Weichert 9; Petra Hoknecht 10;

Christian Grah 11; Achim Rittmeyer 12; Frank Griesinger 13; Michael Thomas 14

1University Hospital Frankfurt, Frankfurt a.M., Deutschland

2Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland

3MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss, Neuss,

Deutschland

4Gemeinschaftspraxis für Hämatologie und Onkologie Dortmund, Dortmund,

Deutschland

5MVZ West GmbH Würselen Hämatologie-Onkologie, Würselen, Deutschland

6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland

7iOMEDICO Freiburg, Freiburg, Deutschland

8AIO-Studien-gGmbH, Berlin, Deutschland

9Technical University of Munich, Institute of Pathology, München, Deutschland

10Niels-Stensen-Kliniken Franziskus-Hospital Harderberg, Georgsmarienhütte,

Deutschland

11Gemeinschaftskrankenhaus Havelhöhe gGmbH, Berlin, Deutschland

12Lungenfachklinik Immenhausen, Immenhausen, Deutschland

13Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland

14Internistische Onkologie der Thoraxtumoren, Thoraxklinik im

Universitätsklinikum Heidelberg, Translational Lung Research Center

Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),

Heidelberg, Deutschland

Purpose: Treatment guidelines for stage IV NSCLC recommend strati-

ed treatment according to biomarker testing results. We used CRISP to

evaluate treatment and outcome of patients (pts) with PD-L1-expressing

tumors.

Methods: Currently 163 centers in Germany have recruited over 4255 pts

at start of 1st-line who will be followed until death or end of project. Data

from 2204 pts recruited by 133 centers between 12/2015 and 06/ 2018

was analyzed regarding PD-L1 testing, treatment and outcome. Progres-

sion-free survival (PFS) was determined in patients being ≥1 year under

observation (recruited until June 30th 2017 (n=906), outcome sample,

(ous)).

Results: Test rates for PD-L1 increased from 25% (2016) to 75% (2018) in

pts with non-squamous tumors (n=1732), and from 20% (2016) to 62%

(2018) in pts with squamous tumors (n=472). PD-L1 TPS was ≥50% in

16% of pts, 1-49% in 18% of pts, and <1% in 7% of pts, while 3%/12% of

pts were classied by pathologists as PD-L1 positive/negative with TPS

not specied. In 9% and 4% an EGFR or ALK alteration was also detected,

respectively.

Of all pts with PD-L1 TPS≥50% 70% received pembrolizumab-based 1st-

line treatment, 21% chemotherapy and 9% another/targeted therapy. At

database cut, 20% had started 2nd-line, 19% had died prior to a 2nd-line

and remaining pts were still in 1st-line. In the ous, median PFS of all pts

with PD-L1 positive tumors was 4.4 months (62% events, 95%-CI 3.5-5.5

months, n=185), in pts with PD-L1 TPS≥50% (n=83) so far 53% had a

progression aer 1st-line. In total, 49% of pts with PD-L1 positive tumors

and 41% of pts with PD-L1 TPS≥50% had died (ous).

Conclusions: Testing for PD-L1 has been quickly integrated into routine

care diagnostics. e majority of pts with PD-L1 positive tumors and a

TPS≥50% receive an immune-oncology therapy. e impact of these

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novel targeted treatment approaches on the outcome of pts will be subject

of future analyses.

Disclosure Statement: None of the authors has declared a conict of interest

regarding the subject of this work.

395

Patients with Metastatic Non-Small Cell Lung Cancer without

Molecular Alterations or PD-L1 Expression in Germany.

Treatment and First Outcome from The Prospective German

Registry Platform Crisp (AIO-TRK-0315)

Frank Griesinger 1; Wilfried E E Eberhardt 2; Harald-Robert Bruch 3;

Jacqueline Rauh 4; Eyck von der Heyde 5; Norbert Marschner 6;

Martina Jänicke 7; Annette Fleitz 7; Lisa Spring 7; Jörg Sahlmann 7;

Aysun Karatas 8; Annette Hipper 8; Wilko Weichert 9; Parvis Sadjadian 10;

Martin Metzenmacher 11; Wolfgang Gleiber 12; Martin Sebastian 12;

Michael Thomas 13

1Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Deutschland

2Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Deutschland

3Praxiskooperation Bonn-Euskirchen, Bonn, Deutschland

4GIM - Gemeinschaftspraxis Innere Medizin, Witten, Deutschland

5Onkologische Schwerpunktpraxis Hannover, Hannover, Deutschland

6Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg, Deutschland

7iOMEDICO Freiburg, Freiburg, Deutschland

8AIO-Studien-gGmbH, Berlin, Deutschland

9Technical University of Munich, Institute of Pathology, München, Deutschland

10Johannes Wesling Klinikum Minden, Minden, Deutschland

11Universitätsklinikum Essen (AöR), Essen, Deutschland

12University Hospital Frankfurt, Frankfurt a.M., Deutschland

13Internistische Onkologie der Thoraxtumoren, Thoraxklinik im

Universitätsklinikum Heidelberg, Translational Lung Research Center

Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL),

Heidelberg, Deutschland

Purpose: Guidelines for stage IV NSCLC recommend stratied treatment

by biomarker test results. We used CRISP to evaluate treatment and out-

come of patients (pts) in whom neither targetable molecular alterations

nor any PD-L1 expression were detected.

Methods: Currently 163 sites in Germany have recruited >4255 pts at start

of 1st-line who will be followed until death or end of project. Data from

2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed.

ese pts started treatment prior approval of immune checkpoint inhibi-

tors (ICI) for this group of pts. Progression-free survival (PFS) was deter-

mined in pts ≥1 year under observation (recruited until 06/2017 (n=906),

outcome sample (ous)).

Results: 6% of pts with non-squamous (nsq) and 35% with squamous (sq)

tumors received no type of biomarker testing prior to start of 1st-line, and

in 49% and 36% no targetable alterations or any PD-L1 expression were

detected. us, 55% and 71% of pts (nsq/sq) were eligible for chemother-

apy (ctx) but no type of targeted therapy at start of 1st-line.

In 1st-line, pts received carboplatin- (55%) or cisplatin-based ctx (24%),

13% targeted therapy (e.g. ICI in trial, switch to TKI but test result not yet

documented).

At database cut, 33% of all pts had started 2nd-line, 24% had died prior to a

2nd-line and remaining pts were still in 1st-line. In the ous, median PFS was

5.0 months (66% events, 95%-CI 4.5-5.5 months, n=457) for nsq tumors

and 4.5 months (66% events, 95%-CI 3.4-5.3 months, n=154) for sq tu-

mors. In total 55% of pts with nsq and 53% of pts with sq tumors had died.

Conclusions: Despite break-throughs with targeted therapies and high

test rates in routine care, the majority of pts do not qualify for targeted

therapy. First outcome results indicate that prognosis is poor in these pts.

Outcome will hopefully improve in the cohort now treated with ctx-ICI

combination.

Disclosure Statement: None of the authors has declared a conict of interest

regarding the subject of this work.

399

Caspian: Os Results from a Randomised Phase 3 Study

of First-Line Durvalumab ± Tremelimumab + Chemotherapy

in ES-SCLC

Niels Reinmuth 1; Luis Paz-Ares 2; Yuanbin Chen 3; Katsuyuki Hotta 4;

Dmytro Trukhin 5; Galina Statsenko 6; Maximilian J Hochmair 7;

Mustafa Özgüroğlu 8; Jun Ho LI 9; Oleksandr Voitko 10; Artem Poltoratskiy 11;

Santiago Ponce 12; Francesco Verderame 13; Libor Havel 14;

Igor Bondarenko 15; Andrzej Kazarnowicz 16; György Losonczy 17;

Nicolay V Conev 18; Jon Armstrong 19; Natalie Byrne 19; Norah Shire 19;

Haiyi Jiang 19; Jonathan Goldman 20; Jürgen Alt 21

1Asklepios Fachkliniken München-Gauting, Gauting, Deutschland

2Hospital Doce de Octubre, Medical Oncology Department , Madrid, Spanien

3Cancer and hematology centers of western Michigan - Muskegon, Norton

Shores, United States

4Okayama University Hospital, Center for Innovative Clinical Medicine,

Okayama, Japan

5Municipal Institution Odessa Regional Oncology Dispensary, unit of

dispensary-polyclinic department, Odesa, Odes’ka oblast, Ukraine

61st Hospital City Clinical, Novosibirsk, Russland

7Otto-Wagner-Spital, Wien, Österreich

8University-Cerrahpaşa, Cerrahpaşa School of Medicine, Fatih/Istanbul, Turkey

9Changwon Samsung Medical Center, Division of Hemato-Oncology,

Department of Internal Medicine, Changwon, Südkorea

10Kyiv City Oncology Hospital, Kyiv, Ukraine

11N. N. Petrov Institute of Oncology, St Petersburg, Russland

12Hospital Universitario 12 de Octubre, Medical Oncology, Madrid, Spanien

13Humanitas Catanese Center of Oncology, Catania, Italien

14Thomayer’s Hospital, 1st Faculty of Medicine of Charles University,

Prague, Tschechien

15Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine

16Tuberculosis and Lung Disease Hospital, Olsztyn, Poland

17Complejo Hospitalario Universitario A Coruña, Coruno, Spanien

18Medical University of Varna, Varna, Bulgaria

19AstraZeneca, Gaithersburg, United States

20University of California, Los Angeles, United States

21Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik, Mainz,

Deutschland

Purpose: Immune checkpoint blockade targeting the PD-1/PD-L1 pathway

in combination with platinum-based chemotherapy (CT) has demonstrated

improved clinical outcomes in patients (pts) with extensive-stage small-cell

lung cancer (ES-SCLC). Treatment with durvalumab (D), a selective, high-af-

nity, human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80, and

tremelimumab (T), a selective human IgG2 mAb against CTLA-4, may pro-

vide possible additive or synergistic eects. Durvalumab demonstrated dura-

ble clinical activity and had a manageable safety prole both as monothera-

py and in combination with tremelimumab in pts with pretreated ES-SCLC

(NCT01693562; NCT02261220; NCT02937818). CASPIAN (NCT03043872)

is a randomised, multicentre, open-label, sponsor-blind, Phase 3 study of

Durvalumab ± Tremelimumab in combination with etoposide and plati-

num-based CT (EP) as rst-line treatment for pts with ES-SCLC.

Methods: In total, 804 pts were randomised 1:1:1 to receive D 1500 mg +

T 75 mg + EP q3w for 4 cycles, followed by D 1500 mg q4w until disease

progression (PD), with one additional dose of T given post EP (Arm 1); D

1500 mg + EP q3w for 4 cycles, followed by D 1500 mg q4w until PD (Arm

2); or EP q3w for 4–6 cycles with prophylactic cranial irradiation if indicat-

ed (Arm 3). Randomisation was stratied by platinum-based CT in cycle 1

(carboplatin vs cisplatin). Pts had histologically or cytologically document-

ed ES-SCLC, WHO/ECOG PS 0 or 1 and were suitable to receive rst-line

platinum-based CT. e primary endpoint was overall survival (OS) for D

± T + EP versus EP. Secondary endpoints included progression-free sur-

vival (PFS); objective response rate; landmark OS and PFS rates; safety and

tolerability; pharmacokinetics; immunogenicity; quality of life.

Results: Results will be presented at WCLC 2019 including OS, key sec-

ondary endpoints, safety and tolerability.

Conclusions: Not applicable.

Reference:

1. Paz-Ares, L. et al., WCLC 2019, Barcelona, #2265

Disclosure Statement: Funding by AstraZeneca

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409

Clinical and Molecular Predictors for The Development

ofEGFR T790M at Failure of First- or Second-Generation

EGFR Inihibitors

Petros Christopoulos 1, 2; Anna-Lena Volckmar 3; Farastuk Bozorgmehr 2, 4;

Nikolaus Magios 4; Jonas Kuon 4; Martina Kirchner 3; Daniel Kazdal 3;

Volker Endris 3; Tilmann Bochtler 4; Felix Herth 2, 4; Claus-Peter Heussel 2, 4;

Hauke Winter 2, 4; Thomas Muley 2, 4; Michael Meister 2, 4; Stefan Rieken 5;

Jürgen R. Fischer 6; Martin Faehling 7; Helge G. Bischo 4;

Albrecht Stenzinger 2, 3; Michael Thomas 2, 4

1Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland

2Translational Lung Research Center Heidelberg, member of the German Center

for Lung Research (DZL)

3Institute of Pathology Heidelberg, Heidelberg, Deutschland

4Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland

5Radioonkologie und Strahlentherapie, Heidelberg, Deutschland

6Onkologie / Krebsheilkunde mit Palliativmedizin, Lungenklinik Loewenstein,

Löwenstein, Deutschland

7Klinik für Kardiologie, Angiologie, Pneumologie, Klinikum Esslingen, Esslingen,

Deutschland

Purpose: Approximately half of epidermal growth factor receptor

(EGFR)+ non-small cell lung cancer (NSCLC) patients failing rst- or sec-

ond-generation EGFR inhibitors (TKI) feature EGFR T790M mutations

and sensitivity to osimertinib, but it is unclear at present which factors

determine this constellation.

Methods: We retrospectively analyzed EGFR+ NSCLC patients that un-

derwent T790M testing at the time of TKI failure at our institutions.

Results: EGFR T790M testing was performed for 182 cases using liquid

biopsies (n=53), tissue rebiopsies (n=110) or both (n=19). Median age

was 64 years with a predominance of female (65%) never-/light-smok-

ers (69%). A positive T790M result was noted in 101/182 patients (55%)

and followed by treatment with osimertinib in 75/101, resulting in a sig-

nicantly longer overall survival (52 vs. 30 months from start of rst-line

treatment, logrank p=0.001). Detection of T790M was positively associ-

ated with presence of EGFR exon 19 deletions (67% vs. 35% in del19+ vs.

del19- cases, p<0.001), and negatively associated with EGFR L858R (48%

vs. 65%, p=0.047), “rare” EGFR mutations (18% vs. 60%, p=0.001) and

presence of co-mutations at baseline in the 38-42 genes covered by our

NGS panel, including TP53 (42% vs. 58%, p=0.042). No signicant re-

lationship was noted with patient sex, age, smoking status, initial ECOG

performance status, histology, previous nonmetastatic NSCLC, pattern

of metastatic spread, lymphocyte-to-neutrophil ratio, use of palliative ra-

diotherapy or surgery, but T790M+ cases were slightly enriched among

patients with rst-line TKI treatment duration > 1 year (63% vs. 48%,

p=0.035).

Conclusions: Acquired EGFR T790M mutations under rst- or sec-

ond-generation EGFR inihibitors are an important prognostic factor with

major therapeutic relevance, but their development cannot be reliably

predicted at present. eir associations with the type of EGFR mutation

and presence of co-mutations suggest that deeper molecular proling

might facilitate identication of more accurate biomarkers.

411

Osimertinib vs Comparator EGFR-TKI As First-Line Treatment

for EGFRM Advanced NSCLC (Flaura): Final Overall Survival

Analysis

Niels Reinmuth 1; Helge Bischo 2; Sabine Bohnet 3;

Christian Meyer Zum Büschenfelde 4; Antje Rückert 5; Rachel Hodge 6;

Yuri Rukazenkov 6; Suresh S. Ramalingam 7

1Asklepios Fachkliniken München-Gauting, Gauting, Deutschland

2Thoraxklinik Heidelberg gGmbH, Heidelberg, Deutschland

3Universitätsklinikum Schleswig‐Holstein, Campus Lübeck, Medizinische

Klinik III - Pulmologie, Lübeck, Deutschland

4St. Vincentius‐Kliniken Karlsruhe, Karlsruhe, Deutschland

5Schwarzwald‐Baar Klinikum Villingen‐Schwenningen GmbH, Villingen‐

Schwenningen, Deutschland

6AstraZeneca, Cambridge, United Kingdom

7Emory University, WinshipCancer Institute, Atlanta, United States

Purpose: Osimertinib, a 3rd generation, irreversible, oral EGFR-TKI po-

tently and selectively inhibits both EGFRm and EGFR T790M and has

demonstrated ecacy in NSCLC CNS metastases. e phase III FLAURA

study (NCT02296125) compared 1st line osimertinib vs comparator EG-

FR-TKI in EGFRm advanced NSCLC. Median progression-free survival

(PFS; primary analysis, DCO 06/12/2017) was signicantly longer with

osimertinib than comparator EGFR-TKI (18.9 vs 10.2 months; p<0.001).

Overall survival (OS) data were immature (25% maturity) at the time of

the primary publication.

Methods: Patients (pts; 556 globally) were randomised 1:1 to osimerti-

nib 80 mg once daily (qd) orally (po) or comparator EGFR-TKI (getinib

250 mg qd or erlotinib 150 mg qd po) and stratied by race (Asian/non-

Asian) and mutation status (Ex19del/L858R). Inclusion criteria: ≥18 years

(Japan: ≥20); treatment-naïve with Ex19del/L858R EGFRm advanced

NSCLC; WHO PS 0–1; neurologically stable pts with CNS metastases

were allowed, provided denitive treatment/steroids were completed for

≥2 weeks. Treatment beyond progression (RECIST 1.1, per investigator)

was allowed if clinical benet continued; pts randomised to the compara-

tor arm could crossover to osimertinib if T790M positive on progression

(BICR conrmed). Primary endpoint: PFS by RECIST 1.1, per investiga-

tor. OS is a secondary endpoint. Safety and tolerability measures included

adverse events (CTCAE v4), clinical and physical assessments.

Results: e data for nal OS analysis (app. 60% maturity across both

arms) is anticipated by 08/2019. At ESMO 2019 median OS, 2- and 3- year

survival rates will be reported for each arm as well as OS across predened

subgroups including race and EGFR mutation type as well as updated

safety data. We will for the rst time provide FLAURA data on the prev-

alence of T790M mutations in dierent molecular subgroups (Ex19del/

L858R) aer progression on 1st line EGFR-TKI.

Conclusions: Not applicable.

Reference:

1. Ramalingam, SS et al., ESMO 2019, Barcelona, LBA to be submitted

Disclosure Statement: Funding by AstraZeneca

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464

Clinical Characteristics and Outcome of BRAF-Mutated

Advanced NSCLC in Two Large German Lung Cancer Centers

Cedric Preuß 1; Julia Roeper 2, 3; Martin Metzenmacher 1;

Wilfried Eberhardt 1, 4; Ursula Stropiep 3, 5; Katrin Wedeken 3, 5;

Henning Reis 6; Thomas Herold 6; Kaid Darwiche 7; Clemens Aigner 8;

Martin Stuschke 9; Kurt Werner Schmid 6; Markus Falk 3, 10;

Lukas C. Heukamp 3, 10; Markus Tiemann 3, 10; Martin Schuler 1, 4, 11;

Marcel Wiesweg 1, 4; Frank Griesinger 3, 5

1Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum,

Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland

2Innere Medizin-Onkologie, Universitätsmedizin Oldenburg, Pius-Hospital,

Oldenburg, Deutschland

3Lungennetzwerk NOWEL, Oldenburg, Deutschland

4Thorakale Onkologie, Westdeutsches Lungenzentrum, Ruhrlandklinik -

Universitätsmedizin Essen, Universität Duisburg-Essen, Essen, Deutschland

5Hämatologie und Onkologie, Innere Medizin-Onkologie, Universitätsmedizin

Oldenburg, Pius-Hospital, Oldenburg, Deutschland

6Institut für Pathologie, Westdeutsches Tumorzentrum, Universitätsklinikum

Essen, Universität Duisburg-Essen, Essen, Deutschland

7Klinik für Pneumologie, Sektion Interventionelle Bronchologie, Westdeutsches

Lungenzentrum, Ruhrlandklinik - Universitätsmedizin Essen, Universität

Duisburg-Essen, Essen, Deutschland

8Thoraxchirurgie und thorakale Endoskopie, Westdeutsches Lungenzentrum,

Ruhrlandklinik - Universitätsmedizin Essen, Universität Duisburg-Essen, Essen,

Deutschland

9Klinik für Strahlentherapie, Westdeutsches Tumorzentrum, Universitätsklinikum

Essen, Universität Duisburg-Essen, Essen, Deutschland

10Institut für Hämatopathologie Hamburg, Hamburg, Deutschland

11Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort

Essen/Düsseldorf, Deutschland

Purpose: BRAF-mutated non-small cell lung cancer (NSCLC) has been

established as a molecularly dened subentity with specic clinical and

biological characteristics. BRAF mutations can be functionally classied1

(class I: V600x, constitutively active monomer; class II: constitutively ac-

tive dimers; class III: low kinase activity, heterodimers amplifying the RAS

signal). Available kinase inhibitors are eective only for V600x mutations.

Recently, class II/III mutations were associated with adverse prognosis2.

We set out to clinically characterize a cohort of BRAF mutated NSCLC

and compare functional class-specic outcome, including the time before

kinase inhibitors became available.

Methods: Retrospective study in two German lung cancer centers. Pa-

tients were identied by database query and clinical data collected from

the electronic patient charts.

Results: We identied 72 patients (m/f 53/47%, median age 64.7y) di-

agnosed 2010-2019 with advanced NSCLC. Median follow up was 23.9

months. 43% of patients had V600x mutations, 32% class II, 25% class III.

Most patients had a positive smoking history, with a trend towards a high-

er proportion in class II/III patients (81% vs 97%, p=0.1). Only a minority

of patients with V600x mutations received kinase inhibitors (16%), which

have been available only since 2017. Median overall survival (OS) was

13.1 months and diered signicantly compared to a reference control

group of 748 NSCLC patients without BRAF mutations (median OS 22.0

months, HR 1.39, p=0.043). In contrast, median OS upon beginning of

palliative therapy (OSpall) was identical (HR 1.03, p=0.9). In this cohort

with only little inuence of targeted therapy, overall survival by functional

class of the mutation was identical (class I vs. II/III, HR 1.02, p=0.95).

Conclusions: e availability of targeted therapy solely for class I muta-

tions appears to be a major factor contributing to the reported superior

outcome compared to class II/III cohorts.

References:

1. Yao, Z. et al. Nature 548, 234–238 (2017)

2. Dagogo-Jack; I. et al. Clin. Cancer Res. 25; 158–165 (2019)

469

Registrational Results of Libretto-001: a Phase 1/2 Trial of

LOXO-292 in Patients with RET-Fusion-Positive Lung Cancer

Jürgen Wolf

Uniklinik Köln, Innere Medizin I, Köln, Deutschland

Purpose: LOXO-292 is a highly selective RET inhibitor with activity

against RET fusions, activating RET mutations and brain metastases.

Methods: is phase 1/2 study (87 sites, 16 countries) enrolled patients

(pts) with advanced RET-altered solid tumors including RET fusion-pos-

itive (RET+) NSCLC (NCT03157128). LOXO-292 was dosed orally in

28-day cycles. Phase 1 established MTD/RP2D (160mg BID). Phase 2

enrolled pts to 1 of 6 cohorts based on tumor type, RET alteration & pri-

or therapies. Primary endpoint: ORR; secondary endpoints: DoR, CNS

ORR, CNS DoR, PFS, and safety.

Results: As of 17-06-19, 253 RET+ NSCLC pts were treated. Primary

analysis set (PAS): rst 105 consecutively enrolled RET+ NSCLC pts who

received prior platinum-based chemotherapy (PBC); 58 pts also received

prior anti-PD-1/PD-L1 agents. Majority of PAS responders were followed

for ≥6 months (m) from rst response. Of remaining 148 pts, 79 were pre-

viously treated with PBC, 55 did not receive prior PBC & 14 did not have

measurable disease at baseline.

Investigator-assessed ORR in PAS: 68% (95%CI 58-76%, n=71/105, 2 PRs

pending conrmation). Responses did not dier by prior therapy (e.g.

anti-PD-1/PD-L1, multikinase inhibitors). Median DoR: 20.3m (95%CI

13.8-24.0) with median follow-up of 8m; as evidenced by wide CI, DoR

estimate is not statistically stable due to low event number (16/69 con-

rmed responders). Intracranial ORR: 91% (n=10/11:2 conrmed CRs, 8

conrmed PRs) for pts with CNS target lesions at baseline.

ORR in treatment-naïve RET+ NSCLC pts: 85% (95%CI 69-95%, n=29/34,

7 PRs pending conrmation). In safety data set of 531 pts, 5 treatment-re-

lated AEs occurred in ≥15% pts: dry mouth, diarrhea, hypertension,

increased AST & ALT. Most AEs: Gr 1-2. Nine (1.7%) pts discontinued

LOXO-292 for treatment-related AEs.

Conclusions: LOXO-292 had marked antitumor activity in RET+ NSCLC

pts & was well tolerated. ese data will form the basis of an FDA NDA

submission later this year.

Disclosure Statement: Previously presented at WCLC 2019.

Jürgen Wolf is author on behalf of the LIBRETTO-001 Investigators

472

Enlarge-Lung: Two-Year Follow-Up of Real-World Patients with

Locally Advanced or Metastatic (Stage IIIB/IV) Squamous and

Non-Squamous Non-Small Cell Lung Cancer (NSCLC) from a

National, Prospective, Non-Interventional Study (NiS Enlarge)

of Nivolumab after Prior Chemotherapy in Germany

Andreas Gröschel 1; Christian Schumann 2; Sylvia Gütz 3; Holger Schulz 4;

Harald Müller-Huesmann 5; Clemens Schulte 6; Rüdiger Liersch 7;

Eyck von der Heyde 8; Verena Wünsch 9; Martin Sebastian 10

1Klinik für Innere Medizin II - Pneumologie und Beatmungsmedizin,

Clemenshospital, Münster

2Klinikum Kempten, Pneumologie, Thoraxonkologie, Schlaf- und

Beatmungsmedizin, Kempten

3Ev. Diakonissenkrankenhaus GmbH, Zentrum für Innere Medizin, Leipzig

4Praxis Internistischer Onkologie und Hämatologie, pioh, Frechen

5Brüderkrankenhaus St. Josef, Klinik für Hämatologie und Onkologie, Paderborn

6Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund

7Gemeinschaftspraxis für Hämatologie und Onkologie, GEHO, Münster

8Studienzentrum am Raschplatz, Hannover

9Bristol-Myers Squibb GmbH & Co KG aA, München

10Medizinische Klinik II, Abteilung Hämatologie, Medizinische Onkologie,

Universitätsklinikum Frankfurt, Frankfurt

Purpose: In two registrational trials, nivolumab showed overall survival

(OS) benet versus docetaxel in pretreated locally advanced or metastatic

NSCLC. ese results have been conrmed by initial data disclosure of

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the German NIS ENLARGE. Here we report mature OS data from the rst

300 patients enrolled in the trial.

Methods: 882 patients with pretreated, locally advanced or metastatic NS-

CLC recruited from 79 cancer care facilities in Germany will be followed

for a period of 5 years from initiation of nivolumab until death, with-

drawal of consent, loss of follow-up/record or end of study. e prima-

ry endpoint is OS. Baseline characteristics are reported using descriptive

statistics. OS from the time of rst nivolumab dose is estimated using the

Kaplan–Meier method. Study was initiated in July 2016.

Results: With the data cut o on July 31st 2019, interim data of the rst

300 patients from the ENLARGE study describe baseline characteristics

and OS of patients with a minimum follow-up of 25 months. We report

OS and response rates for the total population, by histology and other

subgroups of interest (biomarker, ECOG Performance Status, elderly,

metastases).

Conclusions: Real world data provide complementary information about

special patient populations underrepresented in interventional clinical

trials (elderly; poor performance status; comorbidities) and outcomes of

treatment with nivolumab in accordance with the market authorization

approval in Germany.

484

Real World Molecular Testing in Patients with EGFR Mutation-

Positive (EGFRM+) Locally Advanced or Metastatic NSCLC in

Routine Practice in Germany – Interim Results of The Clinical

Registry Panorama

Wolfgang Schütte 1; Christian Schumann 2; Reinhard Büttner 3;

Karl-Matthias Deppermann 4; Niels Reinmuth 5; Michael Thomas 6;

Mark Wroblewski 7; Frank Griesinger 8

1Martha-Maria Krankenhaus Halle-Dölau gGmbH, Klinik für Innere Medizin II,

Halle (Saale), Deutschland

2Klinikverbund Kempten-Oberallgäu gGmbH, Pneumologie, Thoraxonkologie,

Schlaf- und Beatmungsmedizin, Kempten, Deutschland

3Universitätsklinikum Köln, Institut für Pathologie, Köln, Deutschland

4Sana Kliniken Düsseldorf GmbH, Klinik für Pneumologie, Düsseldorf,

Deutschland

5Asklepios Fachkliniken München-Gauting, Department of Thoracic Oncology,

Gauting, Deutschland

6Thoraxklinik im Universitätsklinikum Heidelberg, Internistische Onkologie der

Thoraxtumoren, Heidelberg, Deutschland

7AstraZeneca GmbH, Oncology, Wedel, Deutschland

8Pius-Hospital Oldenburg, Klinik für Hämatologie und Onkologie, Oldenburg,

Deutschland

Purpose: Epidermal Growth Factor Receptor mutations (EGFRm) are

among the most common in patients (pts) with non-small cell lung can-

cer (NSCLC) and can be targeted with EGFR tyrosine kinase inhibitors

(TKIs). Appr. 50% of the pts will acquire resistance by the T790M muta-

tion (T790M). Osimertinib (OSI) is a 3rd generation TKI and standard of

care for pts who developed the acquired resistance by T790M during the

prior TKI treatments.

Methods: PANORAMA (NCT02777658) is a prospective, clinical registry

for pts with EGFRm+ locally advanced or metastatic NSCLC, who pro-

gressed aer prior TKI therapy. Besides others the 2nd interim analysis

(cut-o: 1APR2019) reects data on routine clinical, molecular testing

using descriptive statistics.

Results: Data of 148 evaluable pts were analysed: At diagnosis median

age was 67.5 yrs (min-max 38.4-84.5 yrs), 49 (33%) pts were male and 98

(66%) were diagnosed with NSCLC Stage IV. 124 pts (84%) were tested

for EGFRm at diagnosis, the remaining pts at later time points. At time

of progression on/aer TKI 74/148 pts were tested again, overall re-test

rate aer progression at any time was 76% (113 pts). 107 (95%) out of

these 113 re-tested pts were tested for T790M thereof 73 pts (64%) were

T790M pos (14 pts not yet documented). 55 (75%) pts who were tested

T790M pos aer progression (n=73) were treated with OSI. No dierence

in T790M positivity in the EGFRm subgroups (Ex19Del, L858R) was ap-

parent. Further details on molecular testing will be shown.

Conclusions: e results will help to understand evolving Real World pts

management, treatment patterns and associated outcomes among pts with

EGFRm locally advanced or metastatic NSCLC who have progressed on/

aer TKI therapy. ese data help validating the growing number of data

sets suggesting that only a minority of EGFRm NSCLC pts benet from

sequential TKI-treatment with OSI aer TKI-progression.

Reference:

1. Schumann, C. et al., DGHO-2019, Berlin, #A-1089-0026-00488

Disclosure Statement: Sponsor AstraZeneca

Christian Schumann: Beratungs‐ bzw. Gutachtertätigkeit & Honorare: AstraZeneca

Reinhard Büttner: Honoraria (alle „minor“); Lectures and Advisory boards for

AbbVie, AstraZeneca, Bayer, Bms, Boehringer‐Ingelheim, Illumina, Lilly, MSD,

Novartis, Qiagen, Pzer, Roche; Firmenanteile: Co‐Founder and Scientic Advisor

for Targos Mol. Pathology Inc; Zulassungsverfahren: Testifying Advisor for MSD

in GBA‐assessment for Pembrolizumab, Advisor for Durvalumab

Karl-Matthias Deppermann: Advisory/Consultancy: AstraZeneca, MSD, Boeh-

ringer, Roche, Takeda; Speaker bureau/Expert testimony: AstraZeneca, MSD,

Boehringer, Roche

Niels Reinmuth: AstraZeneca: Advisory/Consultancy; Speaker bureau/Expert

testimony, Travel/Accommodation/Expenses

Unabhängig vom Abstract habe ich Speaker honoraria / advisories and travel

support erhalten von: Bms, Msd, Roche, Abbvie, Takeda und Böhringer erhalten.

Michael omas: Advisory/Consultancy: AbbVie, BMS, Boehringer, Celgene,

Lilly, MSD, Novartis Roche, Takeda; Speaker bureau/Expert testimony: Lilly, MSD,

Takeda; Research grant/Funding (institution): AstraZeneca, BMS, Celgene, Roche;

Travel/Accommodation/Expenses: BMS, Boehringer, MSD, Novartis

Mark Wroblewski: Angestellt bei der Firma AstraZeneca

Frank Griesinger: Beratungs‐ bzw. Gutachtertätigkeit: Astra Zeneca, Boehringer

Ingelheim, Novartis, Pzer, Roche, Bms, Msd, Celgene, Lilly, Takeda, Siemens,

Abbvie, Bayer

Honorare: Astra Zeneca, Boehringer Ingelheim, Novartis, Pzer, Roche, BMS,

MSD, Celgene, Lilly, Takeda, Siemens, Abbvie, Bayer, Finanzierung wissenscha-

licher Untersuchungen: Astra Zeneca, Boehringer Ingelheim, Novartis, Pzer,

Roche, BMS, MSD, Celgene, Lilly, Takeda, Siemens

520

First-Line Immunotherapy in Elderly Patients with Stage

iv Non-Small Cell Lung Cancer: an Early Ecacy and Safety

Assessment

Jonas Kuon 1, 2; Miriam Blasi 1; Heidrun Grosch 1; Petros Christopoulos 1, 2;

Christiane Wiedemann 1; Felix Herth 2, 3; Claus-Peter Heussel 2, 4, 5;

Albrecht Stenzinger 2, 6; Michael Thomas 1, 2

1Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg,

Deutschland

2Translational Lung Research Center Heidelberg (TLRC-H), Member of the

German Center for Lung Research (DZL), Heidelberg, Deutschland

3Pneumology, Thoraxklinik at Heidelberg University Hospital, Heidelberg,

Deutschland

4Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik

at Heidelberg University Hospital, Heidelberg, Deutschland

5Diagnostic and Interventional Radiology, University Hospital Heidelberg,

Heidelberg, Deutschland

6Institute of Pathology, University Hospital, Heidelberg, Heidelberg,

Deutschland

Purpose: Clinical trials have shown benets on both PFS and OS of add-

ing pembrolizumab to standard chemotherapy (CT) in patients with pre-

vious untreated stage IV NSCLC without EGFR or ALK mutations, lead-

ing to approval of rst-line immunotherapy (IO) regardless of the PDL-1

status. Elderly patients are still underrepresented in main clinical trials,

thus there is an unmet need of evaluating safety, ecacy and predictors for

toxicity of novel therapies in this challenging population.

Methods: We retrospectively evaluated clinical features, response rate

(RR) and toxicities of 58 patients aged ≥70 years diagnosed with stage IV

NSCLC treated in our clinic with rst-line IO, both as monotherapy and

in combination with CT, from January 2017.

Results: e mean age was 75.8 years. 17 patients (29%) were treat-

ed with IO plus CT. Among all patients the RR was 59% and the mean

time to response was 6.3 weeks with no signicant dierences between

the two treatment groups (p=0.32 and p=0.07, respectively). 27 patients

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(47%) experienced immune-related adverse events (irAE), 22% of which

reached grade 3, with no signicant dierences comparing the two groups

(p=0.6). e most frequent early-detected irAEs involved thyroid (17% of

patients), lungs (10%) and liver (9%). Neutropenia of grade ≥ 3 occurred

in 4 patients treated with the combination therapy. Treatment was dis-

continued due to toxicity in 7 cases (14%) and 8 patients needed a che-

motherapy dose reduction. Both Charlson Comorbidity Index (CCI) and

age-adjusted CCI were identied as signicant predictors for toxicity of

any type (p=0,026 and p=0,008, respectively).

Conclusions: In this early assessment no signicant dierences regarding

ecacy or toxicity in patients ≥ 70 years old with stage IV NSCLC treated

with either rst-line IO alone or in combination with CT were revealed.

Notably, these preliminary data show a higher irAE rate than expected

based on previous publications. e presence of comorbidities can predict

the toxicity occurrence. We will extend this study to gain deeper insight

into these issues.

544

Mortality After Radiotherapy or Surgery in The Treatment of

Early Stage Non-Small-Cell Lung Cancer: a Population Based

Study on Recent Developments

Christian Ostheimer; Christoph Evers; Franziska Palm; Dirk Vordermark;

Rafael Mikolajczyk; Daniel Medenwald

Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

Purpose: Stereotactic body radiotherapy (SBRT) can achieve high tumour

control with limited toxicity for inoperable early stage non-small-cell lung

cancer (NSCLC) patients. is study aims to assess alterations in the sur-

vival of early stage lung cancer in relation to therapy across recent years.

Methods: e German Epidemiologic Cancer Registries were assessed.

Periods according to availability of SBRT: (1) 2000-2003 (pre-SBRT), (2)

2004-2007 (interim) and (3) 2007-2014 (broad availability of SBRT). To

assess the association of cancer related parameters with mortality, hazard

ratios (HR) from Cox proportional hazards models were computed. To

evaluate the change of treatment related mortality, we performed interac-

tion analyses and the relative excess risk due to interaction (RERI, additive

scale) was computed.

Results: 16,292 patients with UICC stage I NSCLC diagnosed between

2000 and 2014 were analysed. Radiotherapy utilization increased from 5%

in pre-SBRT era to 8.8% aer 2007. In univariate analyses survival in the

whole cohort improved only marginally when 2000-2003 is compared to

2004-2007 (HR=0.92, 95% CI: 0.85-1.01) or 2008-2014 (HR=0.93, 95% CI:

0.86-1.01). Comparing surgery and radiotherapy the interaction analysis

revealed a stronger improvement for radiotherapy (multiplicative scale for

2000-2003 vs. >2007: 0.78, 95% CI: 0.62-0.98), while risk of death was

lower in the surgery group irrespective of period. On an additive scale,

treatment*period interaction revealed a RERI for 2000-2003 vs. >2007 of

-1.18 (95% CI: -1.84, -0.52).

Conclusions: Using population-based data, we observed a survival im-

provement in stage I lung cancer over time. With an increasing utilization

of radiotherapy, a stronger improvement occurred in patients treated with

radiotherapy when compared to surgery.

Reference:

1. Palma D, et al. Impact of Introducing Stereotactic Lung Radiotherapy for El-

derly Patients With Stage I Non–Small-Cell Lung Cancer: A Population-Based

Time-Trend Analysis. J Clin Oncol 2010;35: 5153-5159.

Disclosure Statement: no conict of interest

555

Deciphering The Tumor Immune Microenvironment Based on

CD8+ TiL Density and PD-L1 Expression in Locally Advanced

NSCLC Treated with Concurrent Chemoradiotherapy

Lukas Käsmann 1; Kathrin Gennen 1; Julian Taugner 1; Chukwuka Eze 1;

Olarn Roengvoraphoj 1; Jens Neumann 2; Amanda Tufman 3; Michael

Orth 1; Simone Reu 4; Claus Belka 1; Farkhad Manapov 1

1University Hospital, LMU Munich, Department of Radiation Oncology, Munich,

Deutschland

2University Hospital, LMU Munich, Department of Pathology, Munich,

Deutschland

3University Hospital, LMU Munich, Division of Respiratory Medicine and

Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology

Centre Munich, Munich, Deutschland

4University Hospital Wuerzburg, Department of Pathology, Würzburg ,

Deutschland

Purpose: e prognostic value of the tumor immunity microenviron-

ment (TIME) in multimodal treatment for locally advanced non-small

cell lung cancer (LA-NSCLC) is controversal. e aim of this study was

to investigate the prognostic value of PD-L1 expression on tumor cells

in combination with CD8+ tumor stroma-inltrating lymphocytes (TILs)

density in inoperable LA-NSCLC treated with concurrent chemoradio-

therapy (CRT).

Methods: Data of 31 inoperable LA-NSCLC patients treated with concur-

rent CRT with tumor biopsy samples at initial diagnosis were evaluated.

PD-L1 expression on tumor cells (0% versus ≥1%), CD8+ TILs density

(0-40% vs. 41-100%) and TIME according to classication of Zhang et al.

[1] were evaluated for potential prognostic value in terms of local control,

progressions-free (PFS) and overall survival (OS) as well as correlations

with clinicopathological features investigated.

Results: Median OS was 14months (range: 3-167 months). e OS rates

at 1- and 2 years were 68% and 20%. Local control of the entire cohort

at 1 and 2 years were 74% and 61%, respectively. Median and PFS at 1

and 2 years were 13±1,4 months, 58% and 19%. PD-L1 expression <1%

on tumor cells was associated with improved OS, PFS and local control

in patients treated with concurrent CRT. Evaluation of TIME appears to

be an independent prognostic factor for local control, PFS and OS. e

longest and shortest OS were achieved in patients with typ I (PD-L1neg/

CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57±37

vs. 10±5months, p=0.05), respectively.

Conclusions: Assessment of the tumor immunity microenvironment

(TIME) by PD-L1 expression on tumor cells and CD8+ TILs density is a

predictive biomarker in patients treated with concurrent CRT for inoper-

able LA-NSCLC.

Reference:

1. Zhang Y, Chen L (2016) Classication of advanced human cancers based on

tumor immunity in the MicroEnvironment (TIME) for cancer immunothera-

py. JAMA Oncol 2:1403–1404

Disclosure Statement: Nothing to declare

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579

First Subsequent Treatment After Discontinuation

of Durvalumab in Unresectable, Stage III NSCLC Patients

from PACIFIC

Martin Faehling 1; David Planchard 2; Byoung Chul Cho 3;

Jhanelle Elaine Gray 4; Luis G. Paz-Ares 5; Mustafa Ozguroglu 6;

Augusto E. Villegas 7; Davey B. Daniel 8; David Vicente 9; Shuji Murakami 10;

Rina Hui 11; Takayasu Kurata 12; Alberto Chiappori 13; Ki Hyeong Lee 14;

Yu Gu 15; Catherine Wadsworth 16; Phillip A. Dennis 17;

Scott Joseph Antonia 13; Maike de Wit 18

1Klinikum Esslingen, Esslingen, Deutschland

2Gustave Roussy, Villejuif, Frankreich

3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea

4Lee Mott Cancer Center and Research Institute, Tampa, United States

55Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense

and CNIO, Madrid, Spanien

6Istanbul University-Cerrahpaşa,, Cerrahpaşa School of Medicine, Istanbul,

Turkey

7Cancer Specialists of North Florida, Jacksonville, United States

8Tennessee Oncology, Chattanooga, United States

9Hospital Universitario Virgen Macarena, Sevilla

10Kanagawa Cancer Center, Yokohama, Japan

11Westmead Hospital and the University of Sydney, Sydney, Australien

12Department of Thoracic Oncology, Kansai Medical University Hospital,

Hirakata, Japan

13H. Lee Mott Cancer Center and Research Institute, Tampa, United States

14Chungbuk National University Hospital, Chungbuk National University

College of Medicine, Cheongju, Südkorea

15Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan

16AstraZeneca, Aldeley Park, United Kingdom

17AstraZeneca, Gaithersburg, United States

18Vivantes Klinikum Neukoelln, Berlin, Deutschland

Purpose: In the phase 3 PACIFIC trial of unresectable, stage III NSCLC

patients (pts) without progression aer concurrent chemoradiotherapy

(cCRT), durvalumab (durva) signicantly improved PFS and OS with

similar safety compared to placebo (pbo). We performed exploratory

analyses to characterize 1st subsequent treatment (Tx) aer discontinu-

ation of durva.

Methods: Pts with WHO PS 0/1 and any tumor PD-L1 status were ran-

domized (2:1) 1–42 days aer ≥2 cycles of platinum-based cCRT to durva

10 mg/kg IV or pbo Q2W up to 12 months. Pts were classied by the use

or not of 1st subsequent Tx and category of 1st systemic Tx.

Results: As of Mar 22, 2018, 216/476 (45.4%) and 153/237 (64.6%) in

the durva and pbo arms, respectively, had a RECIST-based PFS event per

BICR (5.7% and 8.4% due to death). 195 (41.0%) and 128 (54.0%) received

1st subsequent Tx, most of which were systemic Tx (158 [33.2%] and 109

[46.0%]): PDCT (16.4% and 19.0%), SCT (8.6% and 8.4%), IT (4.2% and

13.5%) or TT (3.8% and 5.1%); 7.8% and 8.0% received RT only. Time to

1st subsequent therapy or death (TFST) was longer with durva vs pbo (HR

0.58; 95% CI 0.47–0.72; median 21.0 vs 10.4 months). Baseline character-

istics of pts with or without 1st subsequent Tx were similar, and similar

across durva or pbo arms. Best overall response to 1st systemic Tx will be

presented.

Conclusions: Due to longer PFS and fewer progression events with durva

vs pbo, fewer pts on durva required subsequent Tx and, per TFST, much

later. Baseline characteristics were similar for pts with or without 1st sub-

sequent Tx and pts who received 1st systemic Tx, except for pts who re-

ceived TT, as expected due to their molecular prole.

Disclosure Statement: funding by AstraZeneca

581

PD-L1 Expression in Primary Tumour vs Metastatic Samples in

The Phase 3 MYSTiC Study in First-Line Metastatic (m) NSCLC

T. Wehler 1; N. Reinmuth 2; A.-M. Boothman 3; B.C. Cho 4; K.H. Lee 5; A. Luft 6;

M.-J. Ahn 7; M. Scott8; J. Whiteley 8; J. Walker 9; V. Karwe 10;

P. Mukhopadhyay 11; P. Thiyagarajah 11; U. Scheuring 11; N. Rizvi 12;

M. de Wit 13

1Evangelisches Krankenhaus Hamm, Hamm, Deutschland

2Thoracic Oncology Department, Asklepios Lung Clinic, Munich-Gauting,

Deutschland

3Oncology Companion Diagnostics Unit, IMED Biotech Unit, AstraZeneca,

Cambridge, United Kingdom

4Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College

of Medicine, Seoul, Korea

5Medical Oncology, Chungbuk National University Hospital, Cheongju, Korea

6Oncology Department, Leningrad Regional Clinical Hospital, Lunacharskogo

Prospect, Russland

7Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University,

Seoul, Korea

8Diagnostic Development Unit, Precision Medicine, R&D Oncology, AstraZeneca,

Cambridge, United Kingdom

9Oncology Companion Diagnostics Unit, Precision Medicine and Genomics,

IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom

10Biostatistics, AstraZeneca, Gaithersburg, United States

11Global Medicines Development, AstraZeneca, Cambridge, United Kingdom

12Medical Oncology, Columbia University Medical Center, New York, New York,

United States

13Vivantes Netzwerk für Gesundheit GmbH, Berlin, Berlin, Deutschland

Purpose: PD-L1 expression determined by immunohistochemistry (IHC)

can be a useful biomarker to assess the likelihood of benet with an-

ti-PD-1/PD-L1 therapies in pts with mNSCLC. MYSTIC (NCT02453282)

was an open-label, Phase 3 study of durvalumab (D) ± tremelimumab vs

chemotherapy (CT) as rst-line treatment for mNSCLC; stratication

factors for randomisation included tumour cell (TC) PD-L1 expression

(≥25% vs <25%). While not statistically signicant, D showed a clinically

meaningful improvement in OS compared with CT (HR 0.76 [97.54% CI

0.56–1.02], p=0.036) in pts with PD-L1 TC ≥25%. We investigated wheth-

er the use of a primary tumour or metastatic site biopsy to determine PD-

L1 status impacted prevalence of TC ≥25% or clinical benet.

Methods: All pts enrolled in MYSTIC were assessed centrally for TC

staining for PD-L1 from tissue samples acquired <3 months (mo.) prior to

randomisation from either the site of the primary tumour or a distant me-

tastasis. Testing was performed using the VENTANA PD-L1 (SP263) IHC

assay. A post-hoc analysis evaluated prevalence, OS, ORR and duration of

response (DoR) in pts with PD-L1 TC ≥25% as determined using either a

primary tumour or a distant metastatic sample.

Results: Of 1118 pts randomised, 716 (64.0%) provided a primary tumour

sample and 402 (36.0%) provided a metastatic sample. e prevalence of

PD-L1 TC ≥25% assessed using primary vs metastatic samples was 43.0%

vs 44.8% (p=0.569). According to primary or metastatic site, median OS

for D vs CT was 15.8 vs 13.0 mo. (HR 0.81 [95% CI 0.59-1.11]) and 20.5 vs

12.6 mo. (HR 0.65 [95% CI 0.41-1.01]), respectively.

Conclusions: In MYSTIC, PD-L1 TC ≥25% prevalence was similar using

primary or metastatic samples. Favourable HRs for OS with D vs CT were

seen in pts with TC ≥25% expression as determined in either the primary

tumour or a metastatic site. Results should be interpreted with caution

given the retrospective nature of the analysis.

Reference:

1. NCT02453282 (release date: 25 May 2015)

Disclosure Statement: Funded by AstraZeneca

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591

Nationwide Tumor-Biological Testing Survey in Patients

with NSCLC in Germany – Current Results and Development

of Testing Behavior Since 2012

Helmut Ostermann 1; Dieter Ukena 2; Alexander Freitag 3

1University of Munich, Department of Hematology and Oncology, München,

Deutschland

2Bremen East Hospital, Department of Pneumology and Respiratory Medicine,

Bremen, Deutschland

3AstraZeneca, Oncology, Wedel, Deutschland

Purpose: Tumor-biological testing of patients with stage IV non-small-

cell lung cancer (NSCLC) is clinically indicated and endorsed by guide-

lines (with only few exceptions) because it enables the use of companion

diagnostic guided drug therapy from which many patients benet consid-

erably. Molecular testing for the biomarkers EGFR, ALK, ROS and BRAF

and immunohistochemical testing for PD-L1 should therefore be manda-

tory. We want to determine whether testing in Germany is performed as

per guideline recommendation.

Methods: Experienced oncologists in dierent types of health care insti-

tutions (certied lung cancer centers, university and non-university hos-

pitals and oce-based physicians) are asked to answer a questionnaire on

the details of testing. Data are analyzed by explorative analysis. e cur-

rent results are broken down by institution and compared with those from

previous years to analyze the development of test behavior.

Results: Previous surveys by us (in 2012 and in 2016) have shown that

EGFR mutation analysis was employed in clinical routine in 2012 and

increased signicantly by the end of 2016, when the last survey was con-

ducted. However, there is still potential for improvement in Germany in

terms of the optimal use of therapy options. In the last survey the number

of patients tested was 75% for EGFR, 66% for EML4-ALK, 41% for ROS1,

and 14% for BRAF. ese data will again be examined in the new survey

which is currently ongoing. We will present the results and discuss the

development of testing in Germany from 2012 to 2019.

Conclusions: Despite guideline recommendations it appears that there is

still a signicant number of patients in whom tumor-biological testing is

not done and, therefore, access to optimal treatment may not be possible.

e results that will be presented will clarify whether important improve-

ments in the rate of testing have occurred.

Disclosure Statement: is study was supported by Astra Zeneca

Dieter Ukena received honoraria for speaker activities from Amgen, AstraZeneca,

Boehringer Ingelheim, Bristol Myers Squibb, MSD, Roche. He received honoraria

for consulting activities from AstraZeneca, Boehringer Ingelheim, MSD, Takeda.

Alexander Freitag is an employee of AstraZeneca.

594

Evaluation of Combined Biomarkers for Tumor Response to

Immunotherapy (I/O) in Patients with Advanced Non-Small

Cell Lung Cancer (NSCLC)

Hayat Ramdani 1; Markus Falk 2; Stefanie Schatz 2; Lukas C. Heukamp 2;

Markus Tiemann 2; Ed Schuuring 3; Harry Groen 3; Frank Griesinger 1

1Universitätsklinik für Innere-Medizin und Onkologie, Pius Hospital Oldenburg ,

Oldenburg, Deutschland

2Institur für Hämatopathologie Hamburg, Lung cancer network NOWEL ,

Hamburg, Deutschland

3Universiteit Groningen, Dept. Pathology, University of Groningen, Groningen,

Niederlande

Purpose: Immune checkpoint inhibitors have revolutionized NSCLC

treatment. At present, the only established predictive biomarker for I/O

therapy stratication are PD-L1 expression and MSI status. However, the

expression of PD-L1 is limited by heterogeneous expression and even high

expressors not always respond to I/O therapy. e aim of the study is to

evaluate the value of combinations of positive (Tumor Mutational Bur-

den, PD-L1) and negative (a.o. CD73 expression and inactivating STK11

mutations) predictive markers in patients (pts) with advanced NSCLC on

I/O therapy.

Methods: A retrospective study was performed on a cohort of 54 pts with

advanced NSCLC that have been treated with I/O between 2015/2018.

Pts were selected by the availability of tumor tissue and based on tumor

response evaluated by RECIST v1.1 criteria: only patients with durable

tumor response (CR,PR > 6 months) and patients with no tumor response

(PD as best response) were analyzed for biomarkers: hybrid capture NGS

assay for TMB (New Oncology) including STK11 mutations and IHC

tests for PD-L1, CD73 and VISTA. Adjusted Cox regression and ROC

analysis will be performed to evaluate the predictive value of the dierent

biomarkers.

Results: 43/54 pts received nivolumab, 11/54 pembrolizumab in dierent

therapy lines (1st to 5th). 24 pts were dened as having a durable tumor

response (median PFS 44 months, median OS 53 months; p<0.0001) 30

pts as primary progressors (median PFS 2 months, median OS 12 months;

p<0.0001). In 30/54 pts enough material was available for TMB testing. In

13 durable responders median TMB-value was 13.28 mt/Mb versus 11.00

mt/Mb in 17 primary non-responders. STK11 mutations were observed in

3/17 primary non-responders (10%) vs. 0/13 in durable responders (0%).

Additional analyses of the biomarkers will be presented at the meeting

with correlative data of the parameters analyzed.

Conclusions: Our results suggest that integrating several biomarkers in-

cluding positive and negative predictive markers may correlate better with

responses to I/O than PD-L1 and TMB alone.

Disclosure Statement: no COI

604

Screening of Pleural Mesothelioma Cell Lines for Kinase

Activity May Identify New Targets to Overcome of Therapy

Resistance in Patients Receiving Platin-Based Chemotherapy

Sabrina Borchert 1; Pia Maria Suckrau 1; Michael Wessolly 1;

Elena Mairinger 1; Balazs Hegedus 2; Thomas Hager 1; Thomas Herold 1;

Wilfried Eberhardt 3; Jeremias Wohlschläger 1, 4; Clemens Aigner 2;

Agnes Bankfalvi 1; Kurt Werner Schmid 1; Robert Walter 1, 5;

Fabian Dominik Mairinger 1

1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,

Essen, Deutschland

2Department of Thoracic Surgery and Thoracical Endoscopy, Ruhrlandklinik,

West German Lung Centre, University Hospital Essen, University of Duisburg-

Essen, Essen, Deutschland

3Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, University of Duisburg-Essen, Essen, Deutschland

4Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,

Deutschland

5Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University

of Duisburg-Essen, Essen, Deutschland

Purpose: Malignant pleural mesothelioma (MPM) is a rare, predomi-

nantly asbestos-related and biologically highly aggressive tumor leading

to a dismal prognosis. Platin-compounds are standard chemotherapeutic

agents and still a hallmark of chemotherapy for MPM. e reasons for

the rather poor ecacy largely unknown. Kinase activity might inuence

cellular response to these regimes.

Methods: We screened dierent MPM cell lines for overall phosphoryla-

tion signatures as well as kinase activity with respect to cellular response

to cisplatin-based therapeutics in a high-throughput manner using the

highly innovative technique PamGene. Cell state analysis including apop-

tosis, necrosis as well as cell viability was performed by using enzyme-ac-

tivity and uorescent-based assays.

Results: Cisplatin alters phosphorylation aecting cell cycle, migration,

adhesion, signal transduction, immune modulation and apoptosis of cells.

High phosphorylation, especially of ESR1, LAT, PTPN12 and PTPN6

aecting proliferation and the RAS-MAPK-Pathway, leads to platin re-

sistance. In cisplatin-responsive cell lines, phosphorylation of AKT1 and

GSK3B was reduced. Cisplatin-responsive cell lines showed elevated

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phosphorylation levels of JNK1/2/3, but decreased phosphorylation in

cisplatin-resistant NCI-H2452 cells.

Conclusions: Kinase phosphorylation and activity might play a crucial

role in cellular response to cytostatic agents. Cisplatin inuences phos-

phorylation patterns in tested cell lines with distinct features in cispla-

tin-resistant cell lines. Based on our results, the induction of p38 or

JNK1/3, or inhibition of AKT1 by e.g. BIA-6, might have synergistic eect

with platin-based strategies and therefore be a therapeutic approach to in-

duce apoptotic response to cisplatin treatment, thus potentially enhancing

patients’ outcome.

Disclosure Statement: e authors have no conicts of interest to disclose.

606

Impact of Metallothionein-Knockdown on Cisplatin Resistance

in Malignant Pleural Mesothelioma

Sabrina Borchert 1, 2; Pia Maria Suckrau 1; Robert Walter 1, 2, 3;

Michael Wessolly 1, 2; Elena Mairinger 1, 2; Julia Radke 1, 2; Balazs Hegedüs 4;

Thomas Hager 1, 2; Thomas Herold 1, 2; Wilfried Eberhardt 3, 5;

Jeremias Wohlschläger 1, 6; Clemens Aigner 4; Agnes Bankfalvi 1, 2;

Kurt Werner Schmid 1, 2; Fabian Dominik Mairinger 1, 2

1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,

Essen, Deutschland

2German Cancer Consortium (DKTK), Partner Site University Hospital Essen,

Universitätsklinikum Essen, Essen, Deutschland

3Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University

of Duisburg-Essen, Essen, Deutschland

4Department of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik,

University Hospital Essen, University of Duisburg-Essen, Essen, Deutschland

5Department of Medical Oncology, West German Cancer Centre, University

Hospital Essen, University of Duisburg-Essen, Essen, Deutschland

6Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,

Deutschland

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor

with dismal prognosis. Platinum-based chemotherapy is standardly

used for treatment. e expression of metallothioneins (MT) has been

identied as a reason for cisplatin resistance in MPM. We hypothesized

that knockdown of MT expression might improve response to cisplatin

treatment.

Methods: MT expression of three MPM cell lines and the lung broblast

cell line MRC 5, and their sensitivity to cisplatin treatment have been eval-

uated. Knockdown of MT1A, 1B and 2A expression was induced by RNA

interference and subsequently, MT expression was measured using qPCR.

Cell viability, necrosis and apoptosis before and aer incubation with cis-

platin was analyzed.

Results: MT2A gene expression was observed in all MPM cell lines, with

highest expression in NCI H2452 and NCI H2052. Gene expression levels

of MT1A and MT1B were very low or absent. e immunohistochemical

protein expression of MT-I/II correspond to MT2A gene expression lev-

els. Especially for MSTO 211H, a strong induction of MT2A expression

was observed during cisplatin treatment, indicating a platin-dependent

adaption mechanism. Additionally, a MT2A dependent response to cis-

platin treatment was observed, leading to three dierent MT based phe-

notypes. Knockdown of MT2A signicantly induced apoptosis during

cisplatin treatment with strongest induction of apoptosis in each of the

MPM cell lines, but in dierent phenotypes. We observed a therapeutic

meaningful eect of MT2A knockdown and subsequent cisplatin treat-

ment in MSTO 211H cells.

Conclusions: MT2A seems to be part of the underlying mechanism of

cisplatin resistance in MPM. Especially in MSTO 211H cells, major eects

by knockdown of MT2A expression could be observed, verifying our hy-

pothesis of an MT driven resistance mechanism in MPM. Inhibition of

MT2A could be used as a powerful tool to boost response rates to cispla-

tin-based therapy in vitro. ese data carry the potential to boost clinical

outcome and management of MPM in the future.

Disclosure Statement: e authors have nothing to disclose.

607

Early Clearance of Plasma EGFR Mutations As a Predictor

of Response to Osimertinib and Comparator EGFR-TKiS

in the Flaura Trial

Helge Bischo 1; Caicun Zhou 2; Fumio Imamura 3; Ying Cheng 4;

Isamu Okamoto 5; Byoung Chul Cho 6; Meng Chih Lin 7; Margarita Majem 8;

Oliver Gautschi 9; Jhanelle Elaine Gray 10; Michael J. Boyer 11;

Juliann Chmielecki 12; Ryan Hartmaier 13; Krishna Bulusu 13; J Carl Barrett 13;

Rachel Hodge 13; Matilde Saggese 13; Astrid Mckeown 13;

Suresh S. Ramalingam 14; Niels Reinmuth 15

1Thoraxklinik Heidelberg gGmbH, Heidelberg, Deutschland

2Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

3Department of Thoracic Oncology, Osaka International Cancer Institute,

Osaka, Japan

4Department of Oncology, Jilin Province Cancer Hospital, Changchun, China

5Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan

6Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College

of Medicine, Seoul, Südkorea

7Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung

Memorial Hospital, Chang Gung University, Kaohsiung, Taiwan

8Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau,

Barcelona, Spanien

9University of Berne and Cantonal Hospital of Lucerne, Lucerne, Schweiz

10Department of Thoracic Oncology, Mott Cancer Center and Research

Institute, Tampa, United States

11Department of Medical Oncology, Chris O’Brien Lifehouse, Camperdown,

Australien

12Translational Sciences, IMED Biotech Unit, AstraZeneca, Waltham,

United States

13AstraZeneca, Cambridge, United Kingdom

14Winship Cancer Institute, Emory University, Atlanta, United States

15Asklepios Fachkliniken München‐Gauting , Gauting, Deutschland

Purpose: In the FLAURA trial, osimertinib showed superior ecacy to

comparator EGFR-TKIs as rst line treatment for EGFR mutation-posi-

tive (EGFRm) advanced NSCLC. In an exploratory analysis, we investi-

gated clinical outcomes associated with detection of plasma EGFRm at 3

or 6 weeks (wks) aer start of treatment.

Methods: Treatment-naive patients (pts) with EGFRm locally advanced

or metastatic NSCLC were randomized 1:1 to receive osimertinib 80 mg

or comparator EGFR-TKIs (getinib 250 mg QD or erlotinib 150 mg QD).

Plasma EGFR mutation analysis was conducted at baseline (BL), wks 3

and 6 by droplet digital PCR. Clearance was dened as undetectable levels

of EGFRm in ctDNA at wks 3/6, where they were detectable at BL. PFS

was investigated based on early clearance of EGFRm.

Results: In total 489/556 (88%) pts (osimertinib: 244/279; comparator:

245/277) had evaluable ctDNA at BL and wks 3/6. Of these, 342/489 (70%;

osimertinib: 168/244; comparator: 174/245) had detectable BL EGFRm

and were included in this analysis. See table.

Conclusions: Clearance of plasma EGFRm aer 3/6 wks of EGFR-TKI

therapy was associated with a numerical improvement in PFS. e e-

cacy of osimertinib was superior to comparator EGFR-TKIs regardless of

clearance status

References:

Disclosure Statement: funding AstraZeneca

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630

Integrated Biobanking and Tumor Model Establishment

from Lung Cancer Patients Provides Excellent Tools

for Modern Precision Medicine

Christina Mullins 1; Njanja Enz 1; Jana Rol 2; Michael Becker 2;

Michael Linnebacher 3; Wolfgang Jungraithmayr 1

1Thoraxchirurgie, Universitätsmedizin Rostock, Rostock, Deutschland

2epo - experimental pharmacology & oncology berlin-buch GmbH, Berlin,

Deutschland

3Chirurgie, Universitätsmedizin Rostock, Rostock, Deutschland

Purpose: e rst tumor cell line was established in the 1950s, in vivo

models followed suit in the 1960s. e current focus is on patient-derived

models; especially the patient derived xenogras (PDX) are very popular

for preclinical drug development to mimicking clinical trials. In paral-

lel, the generation of large biobanks, enabling individualized therapy ap-

proaches, at least on a patho-molecular level of the tumor, has become

standard in comprehensive cancer centers.

Methods: Patients operated on at the University Medical Center Rostock

from 2010 onward participated in the HROLu collection (HRO: Hanses-

tadt Rostock; Lu: lung cancer). Samples were collected using strict SOP in-

cluding blood, tumor tissue as well as adjacent normal epithelium. Patient

and tumor data including classication, sub-type, and results of model

establishment are the essential pillars.

Results: In total, 39 patients with either a primary lung tumor (n=27) or

a metastasis (n=12) of a primary brain tumor were included so far. e

male-to-female ratio was 1.6: 24 male and 15 female patients. e mean

age at time of surgery was 61 years, ranging from 36 to 80 years. e sub-

type distribution in the primaries was: one small cell carcinoma and 20

adenocarcinomas, 1 squamous cell carcinomas, 1 large cell carcinoma

and 1 adenosquamous and in the metastases: 5 adenocarcinomas, 3 squa-

mous cell carcinomas, 1 large cell carcinoma and 3 not further dened

metastases. Patient-derived tumor model establishment attempts in vitro

were successful for 3/33 (9%); however 12 are still ongoing. A PDX could

be established in 3/5 (60%). Sensitivity of the PDX towards a variety of

therapeutics commonly used in tumor therapy was tested. One PDX was

highly sensitive towards most of the therapeutics tested; one PDX was

highly sensitive towards Gemcitabine and Bevacizumab, the third PDX

was highly sensitive towards Paclitaxel.

Conclusions: ese patient individual tumor models and biobanked ma-

terials represent a valuable basis for translational and preclinical studies.

Disclosure Statement: none to declare

635

Predicting Response and Outcome After Platin-Based

Chemotherapy and New, Targeted Approaches in Malignant

Pleural Mesothelioma

Fabian Dominik Mairinger 1; Sabrina Borchert 1; Michael Wessolly 1;

Elena Mairinger 1; Jens Kollmeier 2; Daniel Christoph 3, 4; Wilfried Eberhardt 3;

Balazs Hegedus 5; Pia Maria Suckrau 1; Thomas Hager 1;

Saskia Roxanne Sydow 6; Henning Ohlig 1; Martine Wyrich 1; Julia Radke 1;

Thomas Herold 1; Thomas Mairinger 7; Clemens Aigner 5;

Kurt Werner Schmid 1; Agnes Bankfalvi 1; Jeremias Wohlschläger 1, 8;

Robert Walter 1, 9

1Institute of Pathology, University Hospital Essen, University of Duisburg-Essen,

Essen, Deutschland

2Institute of Pneumology, Helios Klinikum Emil von Behring, Berlin, Deutschland

3Department of Medical Oncology, West German Cancer Center, University

Hospital Essen, University of Duisburg-Essen, Essen, Deutschland

4Department of Internistic Oncology, Kliniken Essen Mitte, Essen, Deutschland

5Department of Thoracic Surgery and Thoracical Endoscopy, Ruhrlandklinik,

University Hospital Essen, University of Duisburg-Essen, Essen, Deutschland

6Institute of Pathology, Charité Universitaetsmedizin, Berlin, Berlin, Deutschland

7Department of Tissue Diagnostics, Helios Klinikum Emil von Behring, Berlin,

Deutschland

8Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,

Deutschland

9Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University

of Duisburg-Essen, Essen, Deutschland

Purpose: Platin-analoga are the drug of choice for the treatment of

malignant pleural mesothelioma (MPM), resulting in response rates of

merely 6 to 16%. e reasons for the rather poor ecacy largely unknown.

Against the unsatisfactory background, we investigated the impact of

platinum uptake, -metabolism as well as DNA-damage response on

therapy outcome.

Methods: FFPE samples of 236 MPM patients and healthy tissue from

20 patients with spontaneous pneumothorax were used. For function-

al validation, 6 cell lines were analyzed in the same manner. Specimens

were screened by digital gene expression analysis for 366 mRNAs and

800 important miRNAs using NanoString technology. Additionally, 48

selected candidate genes were analyzed in a multiplex manner using the

PlexSet chemistry. Complementary, we discovered gene expression lev-

els of signicant targets via qPCR and protein expression levels via IHC.

Methylation patterns were analyzed of 284 dierent CpG sites via mass

spectrometry (MassARRAY EpiTYPER). To proof casuistic association,

viability, necrosis and apoptosis of all cell lines were analyzed before and

aer incubation with cisplatin. Knock-down of target genes was induced

by RNA interference.

Results: mRNA levels of DDR pathway members (MMR, BER, NER) are

signicantly associated with response to chemotherapy as well as OS and

PFS in MPM patients. Especially genes involved in TP53-mediated DNA

damage recognition, those compiled under the term “BRCAness” as well

as metallothioneins have been identied to mediate tumors’ response

rates against cisplatin-based chemotherapeutic regimes.

Conclusions: Beside modern therapeutic concepts, biomarker strati-

cation is urgently needed concerning nowadays state-of-the-art chemo-

therapeutic to improve and individualize MPM-therapy, saving non-re-

sponders from inecient and side-eect loaded therapy. Our results will

hopefully nd their way into clinical and pathological practice, resulting

in a benet for patients and improved clinical outcome.

Disclosure Statement: e authors have nothing to disclose.

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638

Using German Claims Data to Characterize Real-World

Treatment Patterns in Cancer Patients – The Example of

Crizotinib

Sarina Schwarz 1; Katja Oppelt 1; Ulrike Haug 1, 2

1Leibniz-Institut für Präventionsforschung und Epidemiologie - BIPS, Bremen,

Deutschland

2Fachbereich 11 der Universität Bremen: Human- und

Gesundheitswissenschaften, Bremen, Deutschland

Purpose: To explore the potential of German claims data for characteriza-

tion of real-world treatment patterns in oncology, exemplied by patients

treated with crizotinib which is approved for a certain subtype of non-

small cell lung cancer (LC).

Methods: We used claims data from the German Pharmacoepidemiolog-

ical Research Database (short: GePaRD, information on ~25 million per-

sons), to identify patients with at least one crizotinib dispensation. Each

individual was followed as long as possible, longest 2004 until 2016. We

dened rst line therapy as the rst antineoplastic therapy (inpatient or

outpatient) and subsequent therapies as second or later line therapy. We

described patients regarding age, sex, codes for LC and metastases, num-

ber of crizotinib dispensations, as well as sequence of oncologic therapies

and death.

Results: In total, we identied 348 patients under crizotinib (56% female,

mean age: 58 years). 96% of the patients had a LC diagnosis code and 88%

had metastases coded within 6 months aer the rst LC diagnosis coded

in GePaRD. e mean time between rst LC diagnosis and rst crizotinib

dispensation was 16 months. On average, there were 8 crizotinib dispen-

sations per patient. 25% of patients received crizotinib as rst line therapy,

77% received a non-targeted chemotherapy during the study period and

14% received a non-targeted chemotherapy aer crizotinib discontinu-

ation. 11% of patients died while treated with crizotinib and 16% died

within 3 months aer discontinuing crizotinib therapy.

Conclusions: Using GePaRD we found treatment patterns regarding

crizotinib consistent with other studies and could provide detailed infor-

mation on its utilization. e results underline the potential of German

claims data for real-world monitoring of oncologic drug utilization.

Disclosure Statement: None.

644

Mutations in CTDNA Associated with Sensitivity or Resistance

to Immunotherapy in mNSCLC: Analysis from The Mystic Trial

T. Wehler 1; N. Rizvi 2; B.C. Cho 3; K.H. Lee 4; A. Luft 5; M.-J. Ahn 6; V.

Papadimitrakopoulou 7; J. Heymach 7; S. Peters 8; U. Scheuring 9; H. Si 10;

J. Ye 10; M. Kuziora 10; S. Wu 12; F. Liu 10; B. Higgs 10; N. Reinmuth 11

1Evangelisches Krankenhaus Hamm, Hamm

2Columbia University Medical Center, , New York, United States

3Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Südkorea

4Chungbuk National University Hospital, Chungbuk National University College

of Medicine, Cheongju, Südkorea

5Leningrad Regional Clinical Hospital, St. Petersburg, Russland

6Samsung Medical Center, Seoul, Südkorea

7The University of Texas MD Anderson Cancer Center, Houston, United States

8Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne,

Schweiz

9AstraZeneca, Cambridge, United Kingdom

10AstraZeneca , Gaithersburg, United States

11Asklepios Lung Clinic, München-Gauting, Gauting, Deutschland

Purpose: Tumour mutational burden (TMB) is associated with improved

overall survival (OS) to immunotherapy in patients with metastatic non-

small cell lung cancer (mNSCLC). Prior studies suggest that mutations

in STK11 (LKB1) are associated with resistance to PD-1/PD-L1 inhibitor

monotherapy but the associations between a broader panel of genomic

alterations and response to anti-PD-L1 monotherapy or anti-PD-L1/anti-

CTLA-4 combination therapy are not well characterised. MYSTIC was a

Phase 3 trial of rst-line durvalumab (anti-PD-L1) ± tremelimumab (anti-

CTLA-4) versus platinum-based doublet chemotherapy in patients with

mNSCLC without EGFR mutations or ALK rearrangements. In MYSTIC,

while not statistically signicant, a clinically meaningful improvement

in OS was observed with rst-line durvalumab versus chemotherapy in

patients with mNSCLC and PD-L1 expression in ≥25% of tumour cells

(TC ≥25%). Durvalumab + tremelimumab did not improve OS versus

chemotherapy in patients with PD-L1 TC ≥25%, but showed promising

OS and PFS in an exploratory analysis in patients with blood TMB

(bTMB) ≥20 mut/Mb. Associations between selected gene mutations and

outcomes are being explored in MYSTIC.

Methods: Circulating tumour DNA from baseline blood specimens was

proled using the GuardantOMNI platform. Samples were available from

1003 patients [89.7% of ITT]; of these 943 samples were sequenced. Sur-

vival outcomes and response rates will be analysed in patients with or

without nonsynonymous somatic mutations in KRAS, STK11 (LKB1),

KEAP1 or ARID1A and in association with bTMB status.

Results: Results will be presented on frequency of gene mutations in the

total population. OS and objective response rates will be reported based

on the presence of gene mutations for both the overall population and for

patients who had bTMB above and below designated thresholds.

Conclusions: Conclusions will be based on ndings.

Disclosure Statement: funding by AstraZeneca

652

Adriatic: a Phase III Trial of Durvalumab +/- Tremelimumab

After Concurrent Chemoradiation for Patients with Limited

Stage Small Cell Lung Cancer

F. Griesinger 1; S. Senan 2; N. Shire 3; G. Mak 3; W. Yao 3; H. Jiang3; M. Thomas 5

1Pius-Hospital Oldenburg, Oldenburg, Deutschland

2Department of Radiation Oncology, Vrije Universiteit Amsterdam, Cancer

Center Amsterdam, Amsterdam, Niederlande

3AstraZeneca, Gaithersburg, MD, Gaithersburg, United States

5Thoraxklinik am Universitätsklinikum Heidelberg, Universitätsklinikum

Heidelberg, Heidelberg, Deutschland

Purpose: Limited stage small-cell lung cancer (LS-SCLC), which represents

30% of newly diagnosed SCLC, remains an area of high unmet medical need.

Standard of care, which has not changed for several decades, consists of curative

intent platinum-based chemotherapy concurrent with radiotherapy (cCRT)

followed by prophylactic brain irradiation (PCI) and observation. Despite

good response to cCRT, outcomes remain poor, with median progression-free

survival (PFS) 15 months and overall survival (OS) 25 months. Durvalumab

(D) is a selective, high-anity, human IgG1 monoclonal antibody (mAb) that

blocks programmed cell death ligand-1 binding to programmed cell death-1

and CD80. Tremelimumab (T) is a selective human IgG2 mAb against CTLA-

4. D demonstrated a PFS and OS advantage over placebo in locally advanced

NSCLC following cCRT. D and D + T demonstrated a tolerable safety prole

and antitumour activity in pretreated extensive stage SCLC. e ADRIATIC

trial (NCT03703297) will assess if treatment with D + T is benecial vs placebo

in patients (pts) with LS-SCLC who have not progressed following cCRT.

Methods: ADRIATIC is a Phase 3, randomised, double-blind, multicentre,

placebo-controlled international trial. Pts (N600) will be randomised 1:1:1 to

receive D + placebo T, D + T, or dual placebo, stratied by Stage (I/II vs III)

and receipt of PCI at the investigator’s discretion (yes vs no). Eligible pts must

have conrmed inoperable Stage I–III LS-SCLC; WHO/ECOG PS 0/1; and

completed 4 cycles of cCRT with a response of stable disease or better within

1–42 days prior to randomisation. Pts will receive the assigned treatment until

clinical, RECIST v1.1-dened progressive disease, intolerable toxicity or for a

maximum of 24 months, whichever comes rst. Primary objectives are PFS

and OS for D + T vs placebo. Key secondary endpoints include health-related

quality of life, and safety and tolerability. Recruitment is ongoing.

Results:

Conclusions:

Reference:

1. Clinical trial identication: NCT0370329

Disclosure Statement: Funded by AstraZeneca

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2018

Index

2018

659

Frequency of Epidermal Growth Factor Receptor (EGFR)

Mutations in Stage IB–IIIA Egfr Mutation Positive Non-Small-

Cell Lung Cancer (NSCLC) After Complete Tumour Resection

M. Reck 1; M. Tsuboi 2; R.S. Herbst 3; T. John 4; M. Majem 5; J. Goldman 6;

S.-W. Kim 7; C.-J. Yu 8; J.E. Abrao Miziara 9; S. Novello 10; D. Urban 11;

C. Akewanlop 12; A. Öztürk 13; B.V. Quang 14; D. Kowalski 15; D. Marmol 16;

M. Marotti 16; G. Laus 16; Y.-L. Wu 17; W. Engel-Riedel 18

1Onkologischer Schwerpunkt, Airway Research Center North (ARCN), Deutsches

Zentrum für Lungenforschung, LungenClinic, Grosshansdorf , Grosshansdorf ,

Deutschland

2Department of Thoracic Surgery and Oncology, National Cancer Center

Hospital East, Kashiwa, Japan

3Medical Oncology, Yale School of Medicine and Yale Cancer Center, New

Haven, CT, United States

4Department of Medical Oncology, Austin Health, Melbourne, Australien

5Medical Oncology Services, Hospital de la Santa Creu i Sant Pau, Barcelona,

Spanien

6 University of California Los Angeles, Los Angeles, CA, United States

7Asan Medical Center, Seoul, South Korea

8Department of Internal Medicine, National Taiwan University Hospital and

National Taiwan University College of Medicine, Taipei, Taiwan

9Department of Thoracic Surgery, Barretos, Brasilien

10Oncology Department, University of Turin, AOU San Luigi, Turin, Italien

11Department of Medical Oncology, Institute of Oncology, Chaim Sheba

Medical Center, Tel Hashomer, aliated to Sackler Faculty of Medicine, Tel Aviv

University, Ramat Gan, Israel

12Division of Medical Oncology, Department of Internal Medicine, Faculty of

Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

13Department of Medical Oncology, Süreyyapaşa Chest Diseases and Thoracic

Surgery Training and Research Hospital, Istanbul, Turkey

14Hanoi Oncology Hospital, Hanoi, Viet Nam

15Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie

Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland

16AstraZeneca, Cambridge, United Kingdom

17Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital

and Guangdong Academy of Medical Sciences, Guangzhou, China

18Klinikum der Stadt Köln gGmbH, Köln, Deutschland

Purpose: Data on the frequency of EGFR mutations in patients (pts) with

NSCLC potentially eligible for adjuvant therapy are limited. Osimertinib,

a 3rd-generation, irreversible, oral EGFR-tyrosine kinase inhibitor (TKI),

potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and

EGFR T790M mutations and has shown ecacy in the CNS. e ADAURA

study (NCT02511106) will assess osimertinib as adjuvant therapy in ear-

ly-stage NSCLC aer complete resection. Here we report frequency of the

most common EGFR activating mutations from pts screened for ADAURA.

Methods: ADAURA is a Phase III, double-blind, randomised, place-

bo-controlled study assessing ecacy and safety of osimertinib vs placebo

in adult pts with mainly non-squamous histology, stage IB–IIIA EGFRm

NSCLC, following complete tumour resection, without or aer adjuvant

chemotherapy. At screening, EGFR mutations associated with EGFR-TKI

sensitivity (ex19del, L858R), alone or in combination with exon 20 inser-

tion, G719X, S768I, T790M or L861Q were centrally assessed from resect-

ed tumour samples using the cobas® EGFR Mutation Test (Roche).

Results: In total, 2447 pts were screened. Median age was 63 years (range

23–88), 54% were female, and 61% were non-Asian. At screening, 1087 (44%)

pts were EGFR mutation positive; 110/2447 (4%) pts had an unknown/une-

valuable test result. Of pts EGFR mutation positive, the most common muta-

tions were ex19del and L858R in 572 (53%) and 458 (42%) pts, respectively;

exon 20 insertion, G719X, T790M, S768I, and L861Q mutations occurred in

28 (3%), 24 (2%), 19 (2%), 11 (1%) and 8 (1%) pts, respectively. Mutations

occurred alone or in combination. A higher proportion of EGFR mutation

positive pts were Asian vs non-Asian (681 [63%] vs 402 [37%]; 4 pts missing)

and female vs male (755 [69%] vs 331 [30%]; 1 pt missing).

Conclusions: is analysis shows a high prevalence of EGFRm mutations

in Asian and female pts with stage IB–IIIA NSCLC following complete

resection, which is consistent with the advanced setting.

Reference:

1. NCT02511106

Disclosure Statement: Funded by AstraZeneca

693

Predictors and Eects of Reduced Chemotherapy Dosing

in Patients with Non-Small Cell Lung Cancer IIIB

Lisa Charlotte Thiesing 1; Norman Karg 1; Wolfgang Brückl 2;

Dieter Würein 2; Joachim Ficker 2; Wolfgang Parsch 2

1Paracelsus Medizinische Privatuniversität, Nürnberg

2Klinik für Innere Medizin 3, Schwerpunkt Pneumologie, Universitätsklinik der

Paracelsus Medizinischen Privatuniversität, Klinikum Nürnberg

Purpose: Dose reductions in chemotherapy occur frequently due to vari-

ous reasons. e ubiquitous opinion is that dose reductions favor a nega-

tive outcome. However, there are only few studies that test this opinion in

respect to lung cancer patients. e aim of this retrospective single-center

study is to identify the most common predictors of dose reductions in

NSCLC IIIB patients and to evaluate the eects thereof.

Methods: e study includes 132 patients treated at the Klinikum Nürn-

berg between 2008 - 2015. Predictors of dose reductions were evaluated

using uni- and multivariate methods and survival statistics were analyzed

using Kaplan-Meier and logrank method.

Results: 48% of the patients (n = 63) experienced dose reductions. Male

gender (p = 0.029), age (p = 0.042), comorbidities (CCI) (p = 0.00) and

palliative intent (p = 0.021) were identied as predictors of initial dose

reductions. Initial dose reductions were independent of ECOG status

and initial laboratory values. Dose reductions later in chemotherapy were

linked to hematologic toxicities. e most common hematotoxicites were

leucopenia (45%) and bi-/pancytopenia (23%). 59% of patients with leu-

kopenia and 33% of patients with bi-/pancytopenia had chemotherapeu-

tic doses reduced consecutively. e comparison between patients with

and without dose reduction showed no signicant dierence in overall

survival (OS) (p = 0.598) and progress-free survival (PFS) (p = 0.340). e

OS of patients with reduced doses was 18.86 (± 18.65) vs. 17.51 (± 16.61)

months and PFS was 15.03 (± 18.14) vs. 12.71 (± 17.60) months.

Conclusions: is study supports the view that hematotoxicities are con-

sidered the most serious side eects. In particular, leukopenia was related to

frequent dose reductions. Contrary to expectations, a reduction in chemo-

therapy dosage did not seem to be associated with a worse prognosis. A pos-

sible explanation is that most studies focus on chemotherapy-sensitive tumor

types. In addition, when several cycles of chemotherapy were performed indi-

vidual dose reduction only slightly inuenced the cumulative dose.

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2018

779

Predictive and Prognostic Role of Pretherapeutic

Bodyplethymography in SCLC Patients

Lilli Lmpert; Amanda Tufman; Diego Kaumann-Guerrero

Hospital of the University of Munich (LMU), Department of internal medicine V,

München, Deutschland

Purpose: About 15 % of all newly diagnosed lung cancers are Small Cell

Lung Cancers (SCLC). Despite intensive research in the last 20 years no

relevant improvement of survival has been achieved for these patients.

Estimation of prognosis is essential for treatment planning and patient

guidance. Lung function testing including bodyplethymography and

measurement of diusion capacity has been shown to be a predictive and

prognostic marker in several malignancies. In this context, this project

aims at investigating the predictive and prognostic role of lung function

testing in SCLC patients.

Methods: 209 SCLC patients diagnosed and treated at a German tertiary

care lung cancer were analysed regarding anthropomorphic characteris-

tics. Pretherapeutic lung function tests (spirometry, bodyplethymography

and diusion capacity) were analysed regarding their impact on response

to rst line treatment and survival. Descriptive and comparative uni- and

multivariate analyses were performed

Results: Pretherapeutic elevated values of total lung capacity as well as

residual volume are signicantly associated with rst line treatment fail-

ure and early mortality. Airway obstruction did not show any signicant

impact of treatment response or survival.

Conclusions: Emphysematic lung disease and hyperination seemed to

be a negative pretherapeutic marker regarding treatment response and

survival. ese easy to obtain and cost-eective parameters allow an addi-

tional prognostic estimation in patients with SCLC. us, pretherapeutic

bodyplethymography should be performed in pretherapeutic assessment

of SCLC patients rather than sole spirometry.

Disclosure Statement: No conicts of interest

780

Inammational Scores Predict Survival in Advanced Lung

Cancer Patients

Philipp Habisch; Amanda Tufman; Rudolf Maria Huber;

Diego Kaumann-Guerrero

Divison of Respiratory Medicine and Thoracic Oncology, Department of Internal

Medicine V and Thoracic Oncology Centre Munich, Ludwig-Maximilians-

Universität, München, Deutschland

Purpose: Newly found correlations between inammation and lung can-

cer have expanded the possibilities for patient therapy and prognosis.

Prognostic scores such as mGPS, CAR, NLR, MLR, PLR, SII, LIPI, PIL or

PNI have already proven their validity in the prognosis of patients.

Methods: We retrospectively analyzed 130 lung-cancer-patients treated

at a German tertiary care lung cancer center between 2015 and 2016. We

extracted data sets from electronic records, analyzed anthropometric data,

pre-therapeutic blood values and prognostic scores. Discriminant analy-

sis was performed to predict Overall Survival (OS) and Progression Free

Survival (PFS).

Results: For PFS the factors albumin (p<0,001), clinical response

(p<0,001), CAR (p<0,001), CRP (p<0,001), ECOG-PS (p<0,001), MCV

(p<0,001), mGPS (p<0,001), MLR (p<0,001), PIL (p<0,001), platelets

(p=0,001), LDH (p=0,003), LIPI (p=0,003), lymphocytes (p=0,018),

NLR (p=0,023), PLR (p=0,026), protein (p=0,035), sex (p=0,035) und SII

(p<0,044) were signicant. Signicant prognostic factors of the OS proved

to be Albumin (p<0,001), clinical response (p<0,001), CRP (p<0,001),

ECOG-PS (p<0,001), LDH (p<0,001), LIPI (p<0,001), MCV (p<0,001),

mGPS (p<0,001), PIL (p<0,001), CAR (p=0,002), protein (p=0,002), MLR

(p=0,009), platelets (p=0,017), PNI (p=0,034) and a found driver muta-

tion (p=0,048) in a univariate analysis. In a multivariate analysis MCV,

protein, MLR and PIL were found as independent predictors for OS.

Conclusions: New, inammation-based prognosis scores have shown that

they can be used to make reliable and independent statements about the

prognosis of patients with advanced lung cancer. Since they can be calcu-

lated easily and cost-eectively, they are an ideal complement to classical

prognostic parameters.

Disclosure Statement: Declarations of interest: none; this research did not receive

any specic grant from funding agencies in the public, commercial, or not-for-

prot sectors.

797

Development of ADrug-RelatedCase-Finding Algorithm for

Identifying Patients with NSCLC and SCLC in a German Claims

Database

Sina Neugebauer 1; Frank Griesinger 2; Sabine Dippel 3;

Stephanie Heidenreich 1; Detlef Chruscz 4; Sebastian Lempfert 5;

Peter Kaskel 1

1MSD SHARP & DOHME GMBH, Haar, Deutschland

2Pius Hospital, University Medicine Oldenburg, Dept. Hematology and

Oncology, University Dept. Internal Medicine-Oncology, Oldenburg,

Deutschland

3MSD Merck Sharp & Dohme AG, Luzern, Schweiz

4CONVEMA Versorgungsmanagement GmbH, Berlin, Deutschland

5HCSL Healthcare Consulting, Norderstedt, Deutschland

Purpose: In total,80–85%ofalllung cancer (LC)are classied as non-

small cell LC (NSCLC) and the remaining 15–20% as small cell LC

(SCLC).Histological ndingsare not included withinICD.

Methods: Aim of thisretrospective surveybased onclaimsdataof the

InGef databasewas tond analgorithm to separate NSCLCfrom SCLC

cases. eanalysis period was2015/16.LCpatients were identied based

on ICD-10 codes C33.& C34.

Results: An analysis population of 3.972 primary LC cases was identied.

Since it is not possible to determine the tumor type ofLCwith the help of

the ICD, in this analysis an attempt was made to assign each case based

on the drug therapy (tx) received. Many of the drugs and its combinations

are only approved or prescribed for the tumor of one or the other cell type.

If no dierentiation was possible, the tumor was classied “undieren-

tiated”.e following drugs weredocumented:(i)NSCLC:5-uoruracil,

avelumab, cetuximab, ipilimumab, folic acid, gemcitabine, mitomycin,

nab-paclitacel, paclitaxel, pemetrexed, vinorelbine, atezolizumab, beva-

cizumab, necitumumab, nivolumab, pembrolizumab, afatinib, ceritinib,

crizotinib, dabrafenib, erlotinib, getinib, nintedanib, osimertinib, treme-

tinib.(ii)SCLC: irinotecan, liposomal irinotecan, trofosfamid, carbopla-

tin, cyclophosphamide, doxorubicin, epirubicin, etoposide, ifosfamid,

lomustin, topotecan, vincristin.Cisplatin is licensed and prescribed for

both LC entities. For carboplatin, an o-label allowance for NSCLC exists.

780of the cases could be allocated to NSCLC, and253 toSCLC, respec-

tively, but 2.939 cases had to be classied“undierentiated”.

Conclusions: is case-nding algorithm is a starting point to separate

between NSCLC and SCLC based on drugs prescribed. However; a lot

of patients remain undierentiated.Reasons arethe wide range of ap-

provals of older chemotx;o label useand undetected coding errors. An

amendment of the DRG System; e.g.; more specic LC codes for NSCLC

and SCLC; is suggested to allow for more specic LC research based on

German claims data.

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2018

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2018

Lymphoma and Plasma Cell Disorders

Vorträge

236

Elevate Tn Phase 3 Study of Acalabrutinib Plus Obinutuzumab

or Acalabrutinib Monotherapy vs Chlorambucil Plus

Obinutuzumab (ClbO) in Subjects with Previously Untreated

Chronic Lymphocytic Leukemia (CLL)

Uwe Martens 1; Je Sharman 2; Versha Banerji 3; Laura Maria Fogliatto 4;

Yair Herishanu 5; Talha Munir 6; Renata Walewska 7; George Follows 8;

Karin Karlsson 9; Paolo Ghia 10; Gillian Corbett 11; Patricia Walker 12;

Miklos Egyed 13; Wojciech Jurczak 14; Gilles Salles 15; Ann Janssens 16;

Florence Cymbalista 17; William Wierda 18; Steven E. Coutre 19;

John M. Pagel 20; Alan P. Skarbnik 21; Manali Kamdar 22; Raquel Izumi 23;

Veerendra Munugala 23; Priti Patel 23; Min Hui Wang 23; Soa Wong 23;

Jennifer Woyach 24; John Byrd 24

1Klinik für Innere Medizin III, SLK-Kliniken Heilbronn GmbH / Klinikum am

Gesundbrunnen, Heilbronn, Deutschland

2Willamette Valley Cancer Institute, Eugene, OR, United States

3Department of Biochemistry & Medical Genetics, University of Manitoba,

Research Institute in Oncology and Hematology, Winnipeg, Kanada

4Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, RS, Brasilien

5Department of Hematology, Tel-Aviv Sourasky Medical Center and Sackler

School of Medicine, Tel-Aviv University,, Tel Aviv, Israel

6Haematological Malignancy Diagnostic Service (HMDS), St James’s Institute of

Oncology, Leeds, United Kingdom

7Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, United

Kingdom

8Department of Haematology, Addenbrooke’s Hospital NHS Trust, Cambridge,

United Kingdom

9Department of Haematology, Oncology and Radiophysics, Skåne University

Hospital, Lund, Schweden

10Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,

Italien

11Department of Medicine, Tauranga Hospital, Tauranga, Neuseeland

12Department of Haematology, Oncology and Radiophysics, Alfred Health-

Monash University, Melbourne, Victoria, Australien

13Department of Hematology, Somogy County Mór Kaposi General Hospital,

Kaposvár, Ungarn

14Department of Hematology, Jagiellonian University Medical College, Krakow,

Poland

15Hospices civils de Lyon, centre hospitalier Lyon Sud, service d’hématologie

clinique, Pierre-Bénite, Frankreich

16Hematology Department, University Hospitals Leuven, Leuven, Belgien

17Bobigny: Hématologie, CHU Avicennes, Bobigny, Frankreich

18Department of Leukemia, University of Texas M.D. Anderson Cancer Center,

Houston, TX, United States

19Stanford University School of Medicine, Stanford, CA, United States

20Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer

Institute, Seattle, WA, United States

21Department of Medicine, John Theurer Cancer Center, Hackensack University

Medical Center, Hackensack, NJ, United States

22Division of Hematology, Hematologic Malignancies and Stem Cell

Transplantation, University of Colorado Cancer Center, Aurora, CO, United States

23Acerta Pharma

24The Ohio State University Comprehensive Cancer Center, Columbus, OH,

United States

Purpose: Acalabrutinib is a highly selective, potent, covalent Bruton

tyrosine kinase inhibitor that has shown clinical benet in patients with

R/R as well as treatment-naïve (TN) CLL. ELEVATE-TN (ACE-CL-007,

NCT02475681), a randomized, multicenter, open-label, phase 3 study

is evaluating the safety and ecacy of acalabrutinib in combination

with obinutuzumab or acalabrutinib monotherapy vs ClbO in TN CLL

patients.

Methods: 535 TN patients with CLL were randomized (1:1:1) into three

arms. Patients in the rst arm received chlorambucil (orally, 0,5 mg/kg at

d1 and 15 of cycle 1 to 6) in combination with obinutuzumab (IV, 100mg

on d1, 900mg on d2, 1000mg on d8 and d15 of cycle 1, 1000mg d1 of cycle

2 to 6). Patients in the second arm received acalabrutinib (orally, 100mg

twice daily until disease progression) in combination with obinutuzumab.

Patients in the third arm received acalabrutinib monotherapy. e prima-

ry endpoint was progression-free survival (PFS) in the acalabrutinib and

obinutuzumab arm compared to the ClbO arm, assessed by an indepen-

dent review committee (IRC), and a key secondary endpoint was IRC-as-

sessed PFS in the acalabrutinib monotherapy arm compared to the ClbO

arm. Other secondary endpoints include objective response rate, time to

next treatment, incidence of adverse events and overall survival.

Results: Data for the primary endpoint and key secondary endpoints

based on a pre-specied interim analysis will be included. e trial has

met its primary endpoint; acalabrutinib in combination with obinutu-

zumab demonstrated a statistically-signicant and clinically-meaningful

improvement in PFS when compared with the chemotherapy-based com-

bination of ClbO. e trial also met a key secondary endpoint showing

acalabrutinib monotherapy achieved a statistically-signicant and clini-

cally-meaningful improvement in PFS compared to ClbO. e safety and

tolerability of acalabrutinib was consistent with its established prole.

Conclusions: Forthcoming; based upon unblinded data results.

Reference:

1. AstraZeneca press release 06/06/19

Poster

115

Collection and Utilization of Hematopoietic Stem Cell

Products in Multiple Myeloma

Felix Krummradt 1; Sandra Sauer 1; Patrick Wuchter 2; Petra Pavel 3;

Eva Klein 1; Anita Schmitt 1; Mark Kriegsmann 4; Karin Jordan 1;

Carsten Müller-Tidow 1; Hartmut Goldschmidt 1, 5; Mathias Witzens-Harig 6;

Katharina Kriegsmann 1

1Universitätsklinikum Heidelberg, Medizinische Klinik V, Heidelberg,

Deutschland

2Medizinische Fakultät Mannheim, Institut für Transfusionsmedizin und

Immunologie, Mannheim, Deutschland

3Blutspendezentrale IKTZ Heidelberg, Stammzell-Labor, Heidelberg,

Deutschland

4Universitätsklinikum Heidelberg Pathologisches Institut: Allgemeine

Pathologie und pathologische Anatomie, Heidelberg, Deutschland

5Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

6Universitätsklinikum Heidelberg, Heidelberg, Deutschland

Purpose: High-dose (HD) chemotherapy and autologous blood stem-

cell transplantation (ABSCT) is the standard of care in multiple myeloma

(MM) for transplant-eligible patients. Up to three HD/ABSCTs may be

given during the course of disease, including late-onset relapse.1 ere-

fore, many transplant centers routinely collect more than one peripheral

blood stem cell (PBSC) gra.2 However, subsequent HD/ABSCTs are of-

ten not performed for a variety of reasons.3

Methods: e collection, storage and disposal practice of PBSC products

in a large cohort of MM patients (n=1,114) during a 12-year period was

analyzed (minimum follow-up time 7 years).

Results: e median number of sucient PBSC transplants per patient

was 3 (range 0-6), those were stored in a median of 3 (range 1-11) cryo-

preserved bags (overall n=3,644). 95% of all patients (n=1,059) underwent

at least one HD/ABSCT. However, more than one ABSCT was performed

in 48% (n=532) of patients. Only a small proportion of PBSC bags (3%,

n=109) was used aer a storage of >5 years. Overall, 23% (n=830) of the

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products were discarded and 16% (n=566) were kept in storage until ref-

erence date (March 2019).

Conclusions: We identied considerable discrepancies between the col-

lection/storage and utilization of PBSCs. is is on the one hand associ-

ated with signicant eorts and costs, on the other hand the disposal may

raise legal and ethical questions. We therefore implemented comprehen-

sive guidelines for systematic re-evaluation of stored PBSC gras at our

institution.

References:

1. Chute JP. Autologous Stem Cell Transplantation for Multiple Myeloma: Unde-

rutilized but Highly Eective. J Natl Cancer Inst 2018.

2. Lisenko K et al. Storage Duration of Autologous Stem Cell Preparations Has

No Impact on Hematopoietic Recovery aer Transplantation. BBMT 2017.

3. Phipps C et al. Utilization of stored autologous PBSCs to support second auto-

logous transplantation in multiple myeloma patients in the era of novel agent

therapy. BMT 2015.

156

Simultaneous Occurrence of Castleman’s Disease and

Plasmocytoma with Progression Into Multiple Myeloma

Associated with POEMS Syndrome

A. Wyrwa 1; U. Rüddel 1; O. Yomade 1; W. Franz 2; H.H. Wacker 2; A.

Hochhaus 1; K.G. Schrenk 1

1Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische

Onkologie, Universitätsklinikum Jena , Jena, Deutschland

2Institut für Hämopathologie Kiel, Kiel, Deutschland

Purpose: Castleman’s disease (CD) is a rare heterogeneous group of

lymphoproliferative disorders. We present an unusual case of a patient

with simultaneous CD and plasmocytoma followed by progression into

multiple myeloma with POEMS syndrome and discuss the diagnostic

criteria as well as the treatment options.

Methods: Case report and review of the literature.

Results: A 67-year old woman presented with weight loss, generalized

sensory neuropathic pain, disseminated hemangiomas of the skin and

enlarged mediastinal lymph nodes. On histology the typical morphology

of CD with hyperplastic lymphoid follicles in combination with a lambda

light chain plasmocytoma was found. Additionally monoclonal gammop-

athy of uncertain signicance of the lambda light chain type was demon-

strated. In the bone marrow plasma cells were below 10 %. e criteria for

POEMS (polyradiculoneuropathy, organomegaly, endocrinopathy, mono-

clonal plasma cell disorder and skin changes) syndrome were initially not

met, due to the absence of peripheral neuropathy on electrophysiological

studies. VEGF serum levels were increased with > 1000 pg/ml (NR <445

pg/ml). HIV and HHV8 were negative. Because of the multicentric pre-

sentation of CD a systemic therapy with the anti-Il-6 antibody siltuximab

was started. Aer 13 months of treatment the patient experienced multi-

ple cerebral thrombembolic events. At the same time progressive disease

was diagnosed and treatment was changed to immunochemotherapy with

6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincris-

tine, prednisone). During the 6th cycle of R-CHOP lambda light chains

increased noticeably. Restaging with lymphadenectomy proved a good

response with complete remission of CD. However bone marrow biopsy

showed progression into multiple myeloma with an increase of plasma

cells up to 60 % and electrophysiological studies revealed peripheral neu-

ropathy corresponding to POEMS syndrome.

Conclusions: is unusual case demonstrates the diagnostic challenges as

well as treatment options in Castleman´s disease and POEMS syndrome.

183

Ascend Phase 3 Study of Acalabrutinib vs Investigator’s

Choice of Rituximab Plus Idelalisib (IDR) or Bendamustine

(BR) in Patients with Relapsed/Refractory (R/R) Chronic

Lymphocytic Leukemia (CLL)

Holger Hebart 1; Paolo Ghia 2; Wojciech Jurczak 3; Andrzej Pluta 4;

Malgorzata Wach 5; Daniel Lysak 6; Tomas Kozak 7; Martin Šimkovič 8;

Polina Kaplan 9; Irina Kryachok 10; Arpad Illes 11; Javier De la Serna 12;

Sean Dolan 13; Philip Campbell 14; Gerardo Musuraca 15; Abraham Jacob 16;

Eric Avery 17; Priti Patel 17; Cheng Quah 18; Wei Liang 18; Jae Hoon Lee 19

1Kliniken Ostalb, Stauferklinikum Schwäb. Gmünd, Zentrum Innere Medizin/

Hämatologie/Onkologie, Mutlangen, Deutschland

2Ospedale San Raaele, Unita Tumori Linfoldi, Dipartimento di Oncoematologia,

Milano, Italien

3Malopolskie Centrum Medyczne, Malpolskie, Poland

4Szpital Specjalistyczny w Brzozowie, Podkarpacki Osrodek Onkologiczny im.

Ks.B. Markiewicza, Podkarpackie, Poland

5Samodzielny Publiczny Kliniczny nr 1 w Lublinie, Klinika Hematoonkologii i

Transplantacji Szpiku, Lubelskie, Poland

6Fakultni Nemocnice Plzen, Plzen-Lochotin, Tschechien

7Fakultni Nemocnice Kralovske Vinohrady, Interni hematologicka klinika,

Prahna, Tschechien

8V.Interni hematologicka klinika, Vychodocesky Kraj, Tschechien

9Dnipropetrovsk City Multield Cöinical Hospital Number 4, City Hematology

Center, Dnipropetrovsk, Ukraine

10National Cancer Instutue, Kiev, Ukraine

11Debreceni Egyetem Belgyogyaszai Klinika, Hematologiai Tanzek, Hajdu-Bihar,

Ungarn

12Hospital Universitario 12 de Octubre Servicio de Hematologia, Centro de

Actividades Ambulatorias, Planta 3, Area D, Madrid, Spanien

13Saint John Regional Hospital, Saint John NB E2L 4L2, Kanada

14Barwon Health, The Andrew Love Cancer Centre, Barwon Health, Geelong,

Australien

15Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori, U.O. di

Oncologia Medica - Oncoematologia, Forli-Cesena, Italien

16The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton,

United Kingdom

17Nebraska Hematology Oncology, Lincoln, NE 68506

18Gachon University Gil Medical Center, Incheon, Korea

Purpose: In this randomized, global, multicenter, open-label Phase 3

study (CL-309; ASCEND; NCT02970318), the ecacy and safety of aca-

labrutinib, a highly selective, potent, covalent Bruton tyrosine kinase in-

hibitor, was evaluated vs investigator’s choice of IdR or BR in R/R CLL.

Methods: Eligible patients (pts) with R/R CLL were randomized 1:1 to

100 mg oral acalabrutinib BID until progression vs IdR (Id 150 mg oral

BID and up to 8 IV infusions of R [375 or 500 mg/m2]) or BR (70 mg/m2

IV B on d1 and 2 and R [375 or 500 mg/m2 IV] on d1 for up to 6 cycles).

e primary endpoint was progression-free survival (PFS) assessed by in-

dependent review committee (IRC).

Results: 310 pts were randomized to acalabrutinib (n=155) or IdR/BR

(n=155 [IdR, n=119; BR, n=36]); median age was 67 y (range, 32-90).

At a median follow-up of 16.1 mo, acalabrutinib signicantly prolonged

IRC-assessed PFS vs IdR/BR (median NR vs 16.5 mo; HR 0.31, 95% CI

0.20-0.49, P<.0001). PFS rates at 12 mo were 88% with acalabrutinib and

68% with IdR/BR. PFS improvement with acalabrutinib (vs IdR/BR) was

seen across subgroups including del(17p), TP53 mutation and Rai stage.

IRC-assessed ORR was not signicantly dierent with acalabrutinib vs

IdR/BR (81% vs 75%, respectively; p<.22). 12-mo OS rates were 94% and

91% (with 15 and 18 deaths) for acalabrutinib and IdR/BR, respective-

ly. 23% of pts randomized to IdR/BR crossed over to receive subsequent

acalabrutinib. Grade ≥3 AEs with acalabrutinib (≥5%) were neutropenia

(16%), anemia (12%) and pneumonia (5%); with IdR (≥15%), neutrope-

nia (40%) and diarrhea (24%); with BR (≥5%), neutropenia (31%), anemia

(9%) and constipation (6%). AEs of interest were atrial brillation (5.2%

of pts on acalabrutinib vs 3.3% on IdR/BR), bleeding AEs (26% vs 7.2%;

including major hemorrhage [1.9% vs 2.6%]), Grade ≥3 infections (15%

vs 24%), and 2nd primary malignancies (excluding NMSC; 6.5% vs 2.6%).

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2018

Conclusions: Acalabrutinib monotherapy signicantly improved PFS

with a more tolerable safety prole compared with IdR/BR in pts with

R/R CLL.

Reference:

1. EHA Library. Ghia P. Jun 16; 2019; 273259; LB2606

185

Treatment Reality of Myeloma Patients 2012-2018 in Germany

Rudolf Weide 1; Holger Schulz 2; Lothar Müller 3; Oswald Burkhard 4;

Ute Braun 5; Tilman Steinmetz 6; Peter Ehscheidt 7; Ingo Tamm 8;

Bernhard Rendenbach 9; Stefan Feiten 10

1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland

2pioh - Praxis Internistische Onkologie und Hämatologie, Frechen/Köln,

Deutschland

3Onkologie UnterEms, Leer/Papenburg/Emden, Deutschland

4Internistische Gemeinschaftspraxis Hämatologie, Onkologie, Palliativmedizin,

Worms, Deutschland

5Gemeinschaftspraxis für Hämatologie und Onkologie, Ludwigshafen,

Deutschland

6MV-Zentrum für Onkologie und Hämatologie, Köln, Deutschland

7Onkologische Praxis Dr. Ehscheidt, Neuwied, Deutschland

8Onkologische Schwerpunktpraxis Kurfürstendamm, Berlin, Deutschland

9Praxis für Hämatologie, Onkologie und Nephrologie, Trier, Deutschland

10Institut für Versorgungsforschung in der Onkologie, Koblenz, Deutschland

Purpose: Survival of Multiple Myeloma (MM) patients has improved

in prospective randomized trials. Real world data concerning treatment

and outcome from unselected patients who receive routine care are not

known.

Methods: Multicentre retrospective analysis of 1,000 unselected MM

patients who were treated between 01/2012 and 12/2018 in 9 communi-

ty-based oncology group practices in Germany. Data were extracted from

patient les into a database and analyzed statistically using SPSS.

Results: So far 770 patients have been documented, 45% were female, 55%

male. Median age was 69 years (25-92). 651 patients (85%) fullled CRAB

criteria for cytoreductive treatment. 1st line treatment consisted of bor-

tezomib+dexamethasone (VD) in 15%, bortezomib+melphalan+dexa-

methasone (VMP) in 14%, bortezomib+cyclophosphamide+dexametha-

sone (VCD) in 10% and lenalidomide+dexamethasone (Rd) in 6%. 23%

received other therapy combinations. 32% were treated with high dose

melphalan and stem cell transplantation (SCT). 2nd line therapy consisted

of Rd in 26%, VD in 13%, VMP in 6%, thalidomide+dexamethasone in

6%, VCD in 5%, carlzomib+lenalidomide+dexamethasone (KRd) in 4%

and bendamustine+dexamethasone in 4%. 13% had high dose melphalan

and SCT. 3rd line therapy consisted of Rd in 25%, VD in 10%, VMP in

5%, VCD in 4%, KRd in 3%, daratumumab in 3%, lenalidomide+dara-

tumumab+dexamethasone in 3% and pomalidomide+dexamethasone in

3%. Median overall survival (OS) of the whole cohort was 95.4 months

(0.6-304.8). OS was strongly dependent on age, comorbidities and ECOG

performance status. Median OS of the age cohorts 25-60, 61-70, 71-75 and

76-92 was 146.5 (2.1-340.8), 112.8 (0.6-201.5), 80.8 (0.6-199.8+) and 52.6

(1.2-124.6) months respectively (p<.001).

Conclusions: MM patients who are treated in routine care receive therapy

as suggested by international recommendations. Survival has improved

compared to historical controls and is strongly dependent on age, comor-

bidities and performance status.

Disclosure Statement: All authors report no conicts of interest

266

Obesity is Associated with an Impaired Survival in Lymphoma

Patients Undergoing Autologous Stem Cell Transplantation

Julius Enßle 1; Sebastian Scheich 1; Victoria T. Mücke 2; Fabian Acker 1;

Lukas Aspacher 1; Sebastian Wolf 1; Anne C. Wilke 1; Sarah Weber 1;

Uta Brunnberg 1; Hubert Serve 1; Björn Steen 1

1Medizinische Klinik II - Hämatologie/Medizinische Onkologie,

Universitätsklinikum Frankfurt, Frankfurt, Deutschland

2Medizinische Klinik I - Gastroenterologie/Hepatologie, Universitätsklinikum

Frankfurt, Frankfurt, Deutschland

Purpose: In relapsed and refractory lymphomas, autologous hematopoi-

etic stem cell transplantation (auto-HSCT) provides a possibly curative

treatment option.1,2 Obesity displays an emerging epidemic risk factor for

global mortality and is associated with an increased mortality in cancer

patients.3,4 To date, there is no uniform data on the impact of obesity on

the outcome of lymphoma patients undergoing auto-HSCT.

Methods: We conducted a retrospective single-center study assessing 119

lymphoma patients who underwent auto-HSCT. Overall survival (OS)

served as primary endpoint whereas progression free survival (PFS), cu-

mulative incidence of non-relapse related mortality (NRM) and cumula-

tive incidence of relapse were analyzed as secondary endpoints.

Results: Obese patients (BMI≥30) unveiled a signicant lower OS (45.3%

vs. 77.9%; p=0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to

non-obese patients at 48 months. e cumulative incidence of NRM dis-

played no signicant dierences while the cumulative incidence of relapse

was signicantly increased in patients with BMI≥30 (66.2% vs. 21.5%;

p<0.001). ere was no signicant dierence in OS between patients with

a BMI<25 and overweight patients (BMI 25-30; 76.1% vs. 80.9%; p=0.585)

whereas patients with BMI≥30 exhibited signicant lower OS when com-

pared to either of both groups (76.1% vs. 45.3%; p=.0.021 and 80.9% vs.

45.3%; p=0.010). Furthermore, in a multivariate analysis, obesity was

identied as an independent risk factor for death (HR 2.231; 95% CI 1.024

to 4.860; p=0.043).

Conclusions: In the present study, we demonstrate that obesity is asso-

ciated with an impaired outcome in lymphoma patients undergoing au-

to-HSCT. Further studies are needed to evaluate the reasons for the higher

relapse rate causing higher mortality in obese patients.

References:

1. Hutchings M, et al. Ann Oncol. 2018

2. Philip T, et al. N Engl J Med. 1995

3. Ng M, et al. Lancet. 2014

4. Renehan AG, et al. Lancet. 2008

Disclosure Statement: e authors declare no conict of interest.

302

Pomalidomide, Cyclophosphamide and Dexamethasone (PCD)

is an Eective Salvage Regimen for Multiple Myeloma (MM)

Patients Relapsed and/or Refractory to Daratumumab

Annamaria Brioli 1, 2; Katia Mancuso 3; Thomas Ernst 1; Inken Hilgendorf 1;

Elena Zamagni 3; Florian Heidel 1; Thomas Stauch 1; Andreas Hochhaus 1;

Marie von Lilienfeld-Toal 1

1Universitätsklinikum Jena, Klinik für Innere Medizin II, Abt. Hämatologie und

Internistische Onkologie, Jena, Deutschland

2Universitätsklinikum Jena, Else Kröner Forschungskolleg AntiAge, Jena,

Deutschland

3Università di Bologna, Policlinico S.Orsola-Malpighi, Istituto di Ematologia e

Oncologia Medica, L. e A. Seràgnoli“, Bologna, Italien

Purpose: Daratumumab (dara) alone or in combination with lenalido-

mide (daraRd) or bortezomib (daraVd) is approved for the treatment of

relapsed and/or refractory MM patients (pts). However, treatment options

for pts progressing on dara are limited, and little data are available on the

ecacy of salvage treatment aer dara.

Methods: e aim was to evaluate the ecacy of PCD as salvage therapy

aer dara. Progression free survival (PFS) and overall survival (OS) were

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2018

Index

2018

calculated from the start of PCD. e median follow-up was 16 months

(mo).

Results: irteen pts treated at Jena University Hospital and at the Serag-

noli Institute of Hematology in Bologna who received at least 1 cycle of

PCD aer dara-failure were included. Median age at the start of PCD was

64 years (range 51-84). ree pts had extramedullary (EM) disease. e

median number of previous lines of therapy was 5 (range 2-9). Twelve pts

had previously been treated with melphalan, 2 pts had received allogene-

ic SCT. All patients had previously received IMiDs (12/13 lenalidomide,

4/13 thalidomide), with 11 pts progressing on IMiD therapy. Twelve pts

received bortezomib and 7/13 carlzomib; 9/12 pts were refractory to

proteasome inhibitors. Dara combinations were: 6 pts dara alone, 5 pts

daraRd and 2 pts daraVd. Seven pts (including 2 pts with EM disease)

had a disease refractory to dara. e median daily dose of pomalidomide

was 4 mg (range 1-4), median doses per cycle of cyclophosphamide was

700 mg/m2 (range 0-1800) and of dexamethasone 160 mg (range 0-320).

e median number of cycles of PCD was 5 (range 1-31); 6 patients are

still on treatment. Overall response rate (≥PR) to PCD was 62% (8/13),

including 2 pts with VGPR and 2 pts with CR. Of the 3 pts with EM dis-

ease, 1 achieved a CR and 1 a minimal response. Responses occurred aer

a median of 2 cycles (range 1-5). Median duration of response was 3 mo

(95% CI 0-9), median PFS and OS were 9 (95% CI 3-15) and 16 (95%

CI 9-23) mo, respectively. Toxicity of grade ≥3 was limited and mainly

hematologic (6/13 pts).

Conclusions: PCD is an eective regimen for dara refractory pts, includ-

ing those with EM disease.

361

Rare Lymphomas – Epidemiology from the Munich Cancer

Registry

Anne Schlesinger-Raab 1; Renate Eckel 1; Kathrin Halfter 1;

Gabriele Schubert-Fritschle 2; Jutta Engel 2

1Tumorregister München am Klinikum der Universität München, Institut für

Medizinische Informationsverarbeitung Biometrie und Epidemiologie,

Ludwig-Maximilians-Universität München, München, Deutschland

2Tumorregister München, Bayerisches Kebsregister - Regionalzentrum

München (LGL) am Klinikum der Universität München, Institut für Medizinische

Informationsverarbeitung Biometrie und Epidemiologie , Ludwig-Maximilians-

Universität, München, Deutschland

Purpose: Rare cancers are dened as cancers with an incidence of less

than 6/100,000. In total they represent 22% of the new cancer cases. Lym-

phomas in total are not rare, but they fragment into many dierent enti-

ties which therefore count as rare. e population-based data herein is

presented to weigh in on the results of randomized clinical trials and to

clarify expectations in the treatment of sporadic diagnoses.

Methods: Nine dierent rare lymphoma entities registered in the catch-

ment area of the Munich Cancer Registry (MCR) 1998-2016 were selected

for presentation: lymphocyte predominant Hodgkin lymphoma, hairy cell

leukemia, Mantle cell lymphoma, Burkitt’s lymphoma, MALT lymphoma,

M. Waldenström, primary lymphoma of the central nerve system, cutane-

ous T-cell lymphoma, and peripheral mature T-cell lymphoma. Incidenc-

es, distributions of patient and tumor characteristics, and survival were

computed per entity, sex, and period of initial diagnosis.

Results: e incidences (ASR ES) range between 0.6/100,000 in Mantle

cell lymphoma and 0.15/100,000 in lymphocyte predominant Hodgkin’s

lymphoma. Men account for 62% of all patients. e median age diers

between 44 years in Burkitt’s lymphoma and 68 years in Morbus Walden-

ström. e 5-year relative survival (as estimation for cancer specic sur-

vival) lies between 35.6% in primary CNS lymphoma and 94.7% in hairy

cell leukemia (94.2% in lymphocyte predominant Hodgkin lymphoma,

61.3% in Mantle cell lymphoma, 64.9% in Burkitt’s lymphoma, 89.8% in

MALT lymphoma, 82.3% in M. Waldenström, 70.7% in cutaneous T-cell

lymphoma, and 42.4% in peripheral mature T-cell lymphoma). Apart

from MALT lymphoma and lymphocyte predominant Hodgkin lympho-

ma men have a better prognosis than women. A noteworthy improvement

in survival over time cannot be shown.

Conclusions: Incidence; age; and outcome in rare lymphomas vary ex-

tremely. e treatment of rare diseases such as these lymphomas should

be expanded by the knowledge of “real-life” population-based data to ad-

just and deliver the patients’ expectations.

392

The Prospective Intersectoral National Cohort Study Myriam

to Study Characteristics, Treatment and Outcome of Patients

with Multiple Myeloma in Germany

Wolfgang Knauf 1; Monika Engelhardt 2; Christoph Losem 3; Jörg Lipke 4;

Christian Kasper 5; Tanja Medinger 6; Leonora Houet 7; Martina Jänicke 7;

Norbert Marschner 8; Tobias Dechow 9; Hermann Einsele 10

1Centrum für Hämatologie und Onkologie Bethanien, Frankfurt a.M.,

Deutschland

2Universitätsklinikum Freiburg, Freiburg i.Br., Deutschland

3MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss, Neuss,

Deutschland

4Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland

5Onkologische Schwerpunktpraxis Hof - Medizinisches Versorgungszentrum,

Hof, Deutschland

6iOMEDICO, Freiburg im Breisgau

7iOMEDICO Freiburg, Freiburg i.Br., Deutschland

8Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br.,

Deutschland

9Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,

Deutschland

10Universitätsklinikum Würzburg, Würzburg, Deutschland

Purpose: erapeutic options for multiple myeloma (MM) have markedly

increased over the last decade and a number of new treatments may be ap-

proved in the near future. MYRIAM is a prospective, intersectoral, nation-

al, longitudinal, multicenter cohort study to document patient and disease

characteristics, treatments, course of disease, including clinical and pa-

tient-reported outcomes and consent to perform translational research.

Methods: Between 2017 and 2021 about 2.000 patients with MM giving

informed consent at the start of their rst or second systemic treatment

will be prospectively recruited in 150 dierent sites, including university

and community hospitals and oce-based practices and will be followed

until death or for a maximum of 5 years. Data will be collected in elec-

tronic case report forms with implemented completeness and plausibility

checks, regularly examined by data managers and randomly monitored.

Patient-reported outcomes will be assessed at the time of recruitment, ev-

ery 3 months for the rst 24 months and every 6 months thereaer, for a

maximum of 5 years altogether using the EORTC-QLQ-C30+MY20 and

the Brief Pain Inventory. Patients will be asked to give informed consent

for future translational research of their unused tumor samples. Annu-

al interim analysis will be performed. e study was approved by local

ethics committees and is registered under clinicaltrials.gov (identier:

NCT03308474).

Results: e rst patient was recruited in September 2017. At the time of

abstract submission (August 2019), 788 patients had been recruited in 103

sites. First results on patient and disease characteristics and initial treat-

ments will be presented.

Conclusions: MYRIAM will for the rst time present prospective, inter-

sectoral, longitudinal data on MM patients in Germany. Data will shed

light to the current state of care and allow identication of unmet medical

needs.

Disclosure Statement: None of the authors has declared a conict of interest

regarding the subject of this work.

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524

Diuse Large B-Cell Lymphoma Patient-Derived Xenograft

Models: Establishment and Treatment Study

Aitomi Bittner 1; Bernadette Brzezicha 2; Sophy Denker 1; Nina Thiessen 3;

Clemens A. Schmitt 1, 3, 4, 5, 6

1Charité - University Medical Center, Department of Hematology,

Oncology and Tumor Immunology, Virchow Campus, and Molekulares

Krebsforschungszentrum, Berlin, Deutschland

2Experimental Oncology & Pharmacology Berlin-Buch, Berlin, Deutschland

3Berlin Institute of Health, Berlin, Deutschland

4Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,

Berlin, Deutschland

5Kepler University Hospital, Department of Hematology and Oncology,

Johannes Kepler University, Linz, Österreich

6Deutsches Konsortium für Translationale Krebsforschung (German Cancer

Consortium), Partner site Berlin, Berlin, Deutschland

Purpose: About 30-40% of the patients diagnosed with diuse large B-cell

lymphoma (DLBCL) will not be cured by standard R-CHOP therapy. De-

spite intense molecular proling eorts, the treatment standard remains

unchanged so far. us, new models such as patient-derived xenogras

(PDX) are pivotal to develop molecularly guided treatment alternatives.

Methods: DLBCL PDX were derived from lymph node extirpations or

core needle biopsies, transplanted subcutaneously into immunodecient

NOG mice, and subsequently passaged to NMRI nu/nu mice. Each gra

was passaged 4 to 5 times to generate a stable model. In addition to histo-

logical analysis, whole genome sequencing (WGS) and RNA sequencing

was performed. Stable PDX models were used for treatment studies.

Results: We successfully established 6 DLBCL PDX models from patients

routinely admitted to our center and exposed to standard induction (i.e.

R-CHO[E]P) or salvage therapy in case of progress, as well as patients

treated within the actively recruiting investigator-initiated trial Imbru-

VeRCHOP (ibrutinib, bortezomib, R-CHOP; PI: Clemens A. Schmitt;

multi-center rst-line trial). We performed WGS and gene expression

proling to monitor lymphoma heterogeneity and clonal evolution at pri-

mary PDX establishment and during subsequent serial passaging. Rem-

iniscent of our ImbruVeRCHOP trial, we conducted a treatment study.

In the cyclophosphamide-resistant models, we were able to show that the

addition of ibrutinib and bortezomib to cyclophosphamide delayed tumor

growth. Next, panel-based targeted re-sequencing will be applied to serial

samples obtained upon treatment exposure to investigate therapy-driven

clonal evolution and emerging drug resistance.

Conclusions: e DLBCL PDX models reect histological and genetic

heterogeneity of the primary DLBCL sample from which they were de-

rived from, and present with varying response patterns to ImbruVeR-

CHOP compounds. Response associations with the clinical outcome of

the respective patients, and with distinct molecular proles will be dis-

cussed at the conference.

640

Non-Interventional Optimob-Study: a Nationwide Evaluation

of Mobilization and Collection of Hematopoietic Stem and

Progenitor Cells in Patients with Multiple Myeloma (MM) and

Lymphoma in Clinical Practice

Nicolaus Kröger 2; Max Bittrich 3; Vladan Vucinic 4; Matthias Grube 5;

Marcus Hentrich 6; Maike de Wit 7; Christian Kunz 8; Bernd Metzner 9;

Andreas Humpe 10

1Universitätsklinikum Hamburg-Eppendorf, Department of Stem Cell

Transplantation , Hamburg, Deutschland

2University Hospital Hamburg-Eppendorf, Department of Stem Cell

Transplantation, Hamburg, Deutschland

3Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II, Zentrum

Innere Medizin (ZIM), Würzburg, Deutschland

4University Hospital Leipzig, Department of Hematology and Cell Therapy,

Leipzig, Deutschland

5University Hospital Regensburg, Department of Internal Medicine III,

Regensburg, Deutschland

6Rotkreuzklinikum München, Department of Internal Medicine III, München,

Deutschland

7Vivantes Clinic Neukoelln, Department of Hematology, Oncology and Palliative

Medicine, Berlin, Deutschland

8Westpfalz-Klinikum GmbH, Department of Internal Medicine 1, Kaiserslautern,

Deutschland

9Klinikum Oldenburg, Department of Hematology and Oncology, Oldenburg,

Deutschland

10Klinikum der Universität München - Campus Grosshadern , Department of

Transfusion Medicine, Cellular Therapeutics and Hemostasiology, München,

Deutschland

Purpose: Autologous stem cell transplantation (ASCT) remains a stan-

dard therapy for MM and lymphoma in eligible patients (pts). A sucient

yield of stem cells is necessary for a successful ASCT. In clinical routine

est. 15% (1) of pts are classied as poor mobilizers (PM) requesting sever-

al apheresis sessions (aph). Stem cells are mobilized with chemotherapy +

G-CSF +/- plerixafor (PLX) or G-CSF +/- PLX.

Methods: Pts. with MM, Non-Hodgkin lymphoma or Hodgkin lympho-

ma eligible for ASCT are included in OPTIMOB. Mobilization and collec-

tion parameters are documented and analyzed in detail. Primary endpoint

of the study is the proportion of PM pts. reaching ≥ 2 mio CD34+ cells /

kg body weight with the 1st apheresis. Pts. are dened as PM if they did

not reach ≥ 20 CD34+ cells / µL before 1st aph., receive PLX at any time

point, did not reach the initially planned stem cell yield or terminated

collection early due to poor mobilization. It is planned to include 1.500

pts to identify 210 PM pts.

Results: Up to now 189 pts from 16 centers are documented. About two

thirds of pts have MM and one third malignant lymphoma. Mean age is

61 years and 40 % of pts are female. Half of pts are classied as PM (n=39)

and 21 out of 80 pts received PLX + G-CSF +/- chemotherapy for mobili-

zation. Furthermore, 19 AEs were reported incl. 2 SAEs.

Conclusions: is ongoing large prospective observational study evalu-

ates stem cell mobilization rates in pts with MM and lymphoma who are

candidates for ASCT. Updated data will be presented at the meeting.

Reference:

1. Wuchter et al. Biol Blood Marrow Transplant 16: 490-499 (2010)

Disclosure Statement: is study is supported by Sano.

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647

Gender Dierences in Hematological Malignancy: The

Experience of Jena University Hospital

Maria Madeleine Rüthrich 1; Jakob Hammersen 1; Paul La Rosée 2;

Lars-Olof Mügge 3; Andreas Hochhaus 1; Marie von Lilienfeld-Toal 1;

Annamaria Brioli 1, 4

1Universitätsklinikum Jena, Klinik und für Innere Medizin II, Abteilung für

Hämatologie und internistische Onkologie, Jena, Deutschland

2Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II, Onkologie,

Hämatologie, Immunologie, Infektiologie und Palliativmedizin, Villingen-

Schwenningen, Deutschland

3Heinrich-Braun-Klinikum, Innere Medizin III Hämatologie, Onkologie und

Palliativmedizin, Zwickau, Deutschland

4Universitätsklinikum Jena, Else-Kröner Forschungskolleg AntiAge, Jena,

Deutschland

Purpose: Cardiological studies showed that female (F) patients (pts)

might be undertreated. Data in hematological malignancies are lacking.

Methods: Aim was to investigate gender dierences in multiple myelo-

ma (MM) and diuse large B-cell lymphoma (DLBCL) pts treated at one

center. e MM and DLBCL databases were retrospectively interrogated.

Analysis included descriptive statistics and survival analyses.

Results: Pts included were: 655 (MM) and 304 (DLBCL). Median obser-

vation was 48 months (mo) in MM and 41 mo in DLBCL. F were 43%

(MM) and 51% (DLBCL). Median age was 62 years (yr) (MM, range 35-

89) and 65 yr (DLBCL, range 20-92), and similar between F and men (M)

(MM p=.14, DLBCL p=.33)

At diagnosis (dg) MM pts had no dierence in disease risk (p=.49), stage

(p=.52), MM type (p=.62), or bone involvement (p=.79). F had lower Hb

(p<.001), less coronary heart disease (p=.006) and COPD (p<.001). In

DLBCL, pts status and disease stage were similar: ECOG ≥2 p=.99, stage

≥III p=.14, IPI ≥3 p=.64. More F had B symptoms (p=.04).

MM pts had no dierence in therapy (tp) administered (number/type)

at dg or at rst relapse, in overall response rate (ORR, F 71% vs M 72%,

p=.43) and in overall survival (OS, F 83 vs M 72 mo, p=.45, 95% CI [63-

89]). is applies to all age groups. High dose tp (HDT) was not aected

by sex. More F had mucositis grade ≥3 (p=0.001). Progression free surviv-

al (PFS) (F 27 vs M 26 mo, p=0.37, 95% CI [23-29]) and OS from HDT (F

83 vs M 74 mo, p=0.90, 95% CI [59-95]) were similar.

In DLBCL, 257 pts received CHOP-like tp. ere was no dierence in

ORR (F 72% vs M 69%, p=.56) or OS (F not reached (NR) vs. M 83 mo,

p=.89, 95% CI [54-112]). Elderly F (60-79 yr) had R-CHOP14 in 40% vs

58% elderly M (p=.04). ORR (F 77.5% vs M 73%, p=.83), OS (F NR vs M

NR, p=.94) and PFS (F NR vs M 72 mo p=.64, 95% CI [17-127]) did not

dier, but R-CHOP14 was superior to 21 in elderly F (PFS NR vs 18 mo,

p=.007 95% CI [9-28]).

Conclusions: Gender does not impact on biology, tp and outcome of MM

pts. In Dlbcl, data suggests that elderly F might be undertreated with a

possible eect on outcome.

Disclosure Statement: AB received honoraria from Takeda; Celgene; Sano and

Janssen; Travel support from Celgene; Takeda; Janssen and Gilead and research

founding from Celgene; MvLT received travel support and research founding from

Janssen; Celgene; Takeda; Gilead; MSD; Oncopeptides and Novartis; the other

authors have no conict of interest to declare

722

Treatment of Patients WiT Refractory Hodgkin Lymphoma

Nadezda Basara; Nikolai Faber; Helge Menzel; Petra Drewniock;

Xenia Sitskaia; Stefan Lukic

St Franziskus Hospital, Academical Hospital of the UKSH, Internal medicine I,

Flensburg, Deutschland

Purpose: e anti-CD30 immunotoxin brentuximab-vedotin and check-

point inhibitors Nivolumab and Pembrolizumab has being used for re-

fractory HL patients as monotherapy and in dierent combinations.

Methods: is presentation summarizes our experience in the treatment

of refractory HL.

Results: We have treated a total of 8 patients with refractory Hodgkin

Lymphoma with Nivolumab or Brentuximab, 6 men and 2 female, 16 to

56 years of age. All patients had ECOG 0, 3-4 lines of therapy, 5 patients

had previous radiation therapy, and 4 patients have been treated with au-

tologous peripheral blood stem cell transplantation (PBSCT). Previous

allogeneic PBSCT has been performed in one patient, and 4 patients have

been treated with brentuximab-vedotin prior to nivolumab. e patients

have been treated with 1-8 cycles of Nivolumab 3mg/kg b.w. two weekly

according to the recommendation from CHECK Mate 205 Phase II Study.

e overall response was excellent, CR in 4 patients and PR in 3 patients.

In one patient, the treatment with Nivolumab was terminated due to Liver

toxicity Grade 2.

Conclusions: Encouraging durability of response in our patients of 75% at

median follow up of 25 months has been described. e safety prole with

AEs mostly grade 1 or 2 was acceptable. Nivolumab is an important new

therapy in patients with refractory HL.

References:

1. Chen R, Gopal AK, Smith SE et al. 5-year survival and durability results of

Brentuximab-vedotin in patients with relapsed or refractory Hodgkin lympho-

ma. Blood 2016; 128:1562

2. Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic

Hodgkin Lymphoma aer failure of autologous hematopoietic cell transplan-

tation: Extendedn Follow-up of multicohort Single-Arm Phase II Checkmate

205Trial J Clin Oncol 2018; 36:1428

Disclosure Statement: no disclosure

769

Acquired Hemophagocytic Lymphohistiocytosis as

Paraneoplastic Syndrome in Lymphoma (LA-HLH): atypical

Presentation of Rare Lymphoma Subtypes Requires an

Aggressive Diagnostic Approach

Sebastian Birndt 1; Thomas Schenk 1; Stefani Parmentier 2;

Markus Schaich 2; Stefan Beckert 3; Harald Reiser 3; Jörg Kalla 4;

Andreas Rosenwald 5; German Ott 6; Jochen Talazko 7; Martin Henkes 8;

Andreas Hochhaus 1; Paul Graf La Rosée 8

1Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland

2Hämatologie, Onkologie und Palliativmedizin, Rems-Murr-Kliniken,

Winnenden, Deutschland

3Klinik für Allgemein- und Viszeralchirurgie, Schwarzwald-Baar-Klinikum,

Villingen-Schwenningen, Deutschland

4Institut für Pathologie, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen,

Deutschland

5Institut für Pathologie, Universitätsklinikum Würzburg, Würzburg, Deutschland

6Abteilung für Pathologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland

7Institut für Radiologie und Nuklearmedizin, Schwarzwald-Baar-Klinikum,

Villingen-Schwenningen, Deutschland

8Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-

Schwenningen, Deutschland

Purpose: Acquired hemophagocytic lymphohistiocytosis (HLH) can be

the initial paraneoplastic syndrome at lymphoma onset. Hyperferritine-

mic fever, cytopenia and splenomegaly are diagnostic hallmarks.

Methods: ree patients registered in www.hlh-registry.org with LA-

HLH requiring emergency diagnostic splenectomy are presented.

Results: 1) A 56 y/o patient with relapsing pneumo-pleuritis without specif-

ic histopathologic features developed full blown HLH. PET-CT showed no

accessible hypermetabolic mass. Respiratory failure requiring ICU-treat-

ment triggered etoposide application leading to clinical stabilization. Diag-

nostic splenectomy was performed revealing T-cell rich diuse large B-cell

lymphoma (DLBCL). e patient was cured by 6 x CHOEP and auto-PBSCT.

2) A 53 y/o male organ transplant patient presented with HLH. PET-CT

indicated dim splenic hypermetabolism. HLH-directed treatment sta-

bilized the patient to allow diagnostic splenectomy. Splenic T-cell lym-

phoma was found and T-NHL-directed CHOEP treatment was initiated.

Follow-up will be presented. 3) A 32 y/o male patient presented with

worsening hyperferritinemic fever, neutropenia, splenomegaly, hypo-

brinogenemia, bone marrow phagocytosis. Abdominal probe excision

revealed hemophagocytosis without specic lymphopathology. Due to

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2018

respiratory failure, dexamethasone/etoposide was initiated. Aer stabi-

lization, diagnostic splenectomy was performed revealing T-cell/histio-

cyte-rich DLBCL. e patient was cured with 8 x R-CHOEP and high

dose chemotherapy with auto-PBSCT.

Conclusions: Rare lymphoma phenotypes, inammatory tissue inltra-

tion and severely compromised patients with multiorgan failure make

lymphoma diagnosis in HLH-patients an extra challenge. To over-

come grim prognosis in LA-HLH, resolute diagnostics on concurrent

HLH-treatment require interdisciplinary coordinated interventions1.

Reference:

1. La Rosée et al., Recommendations for the management of hemophagocytic

lymphohistiocytosis in adults. Blood 2019

Disclosure Statement: e authors declare no COI.

804

Comparative Eectiveness of Triplets ContainIng Bortezomib

(B), Carlzomib (C), Daratumumab (D), or Ixazomib (I) in

Relapsed/Refractory Multiple Myeloma (RRMM) in Routine

Care in The US

Katja Weisel 1; Faith Davies 2; Robert Rifkin 3; Caitlin Costello 4;

Saad Usmani 4; Rafat Abonour 5; Antonio Palumbo 6; Dorothy Romanus 6;

Roman Hajek 7; Evangelos Terpos 8; Dawn Marie Stull 6; Hui Huang 6;

Xavier Leleu 9; Jesus Berdeja 10; Hans Lee 11; Michael Thompson 12;

Mario Boccadoro 13; Jerey Zonder 14; Gordon Cook 15; Noemi Puig 16;

Jorge Vela-Ojeda 17; Tomas Skacel 6; Eileen Farrelly 18; Aditya Raju 18;

Ajai Chari 19

1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

2University of Arkansas for Medical Sciences, Little Rock, United States

3Rocky Mountain Cancer Centers, Denver, United States

4Carolinas Healthcare System,, Charlotte, United States

5Indiana University, Indianapolis, United States

6 Millennium Pharmaceuticals, Takeda Pharmaceutical Company, Cambridge,

United States

7University Hospital Ostrava, Ostrava, Tschechien

8University of Athens School of Medicine, Athens, Griechenland

9CHU la Miletrie, Poiters, Frankreich

10Tennessee Oncology, Sarah Cannon Research Institute, Nashville,

United States

11MD Anderson Cancer Center, University of Texas, Houston, United States

12Aurora Cancer Center, Milwaukee, United States

13Azienda Ospedaliera Citta della Salute e della Scienza, Torino, Italien

14Karmanos Cancer Institute, Detroit, United States

15Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

16Salamanca University Hospital, Salamanca, Spanien

17Hospital de Especialidades Centro Medico Nacional la Raza, Mexico City,

Mexico

18Xcenda, Palm Harbor, United States

19Icahn School of Medicine at Mount Sinai, New York, United States

Purpose: Lack of head-to-head trials of novel agents vs bortezomib-based

triplet regimens (TpRs) renders treatment choice for RRMM dicult,

highlighting a need for real-world (RW) evidence. We conducted a RW

comparative eectiveness analysis of bortezomib (B), carlzomib (C), da-

ratumumab (D), and ixazomib (I) based TpRs in RRMM.

Methods: Patients (pts) with ≥1 prior line of therapy (LOT) initiating a

TpR on/aer 1/1/2014 were followed retrospectively in Optum’s de-iden-

tied US electronic health record database (2007-2018), a general pop-

ulation-representative dataset. Duration of therapy (DOT) and time-to-

next-treatment (TTNT) were estimated using Kaplan-Meier methods and

compared using Cox models.

Results: Among 1432 pts with 1902 pt-LOTs in the B/C/D/I groups

(n=746/522/418/216) median age was 70/65/68/69 yrs; pts with CRAB

symptoms: 82/87/82/64%; pts with high risk disease (del 17p and/or

t(4;14) and/or t(14;16) and/or 1q21 gain): 16/26/20/14%; IMID and/or

PI refractory: 38/84/85/65%, respectively. B/C/D/I TpRs consisted of an

alkylator in 36/26/5/5% or an IMID-backbone in 54/70/60/91%, respec-

tively; 81/60/44/64% pts received B/C/D/I TpRs in LOT 2-3. At median

f/u of 16.3/13.3/8.6/10.2 mos in the B/C/D/I groups, unadjusted median

DOTs were: 6.0/6.0/6.2/8.4 mos and TTNTs were: 9.8/6.7/7.2/11.1 mos,

respectively. In LOT 2-3, unadjusted median DOTs in the B/C/I groups

were: 8.4/6.3/8.4 mos and TTNTs were: 10.8/7.8/12.7 mos, respectively;

and not estimable in the D-triplet group. Adjusted risk of next LOTini-

tiation/death were statistically comparable for all groups overall; in LOTs

2-3, a trend toward lower risk of next LOTinitiation/death for I- vs B-trip-

let groups (adjusted HR: 0.77; P=0.09) was noted.

Conclusions: e adjusted risk of starting next LOT/death for C-, D- or

I- vs B-based triplets was not signicantly dierent in LOTs 2+ overall, but

showed a lower trend in LOTs 2-3 for I-based triplets. Limitations include

residual confounding due to unobserved treatment selection biases that

are inherent to any non-randomized, observational study.

834

Acquired Hemophagocytic Lymphohistiocytosis in Cancer

Patients: Initial Presenting Paraneoplastic Syndrome of de

novo Malignancy or Complication of Immunosuppressive

Cancer Treatment?

Heidi Hengstler 1; Manuela Wenzler 1; Birgitta Vogt 1; Jörg Kalla 2;

Andreas Rosenwald 3; Jochen Talazko 4; Stefan Beckert 5; Thomas Schenk 6;

Sebastian Birndt 6; Andreas Hochhaus 6; Martin Henkes 1;

Paul Graf La Rosée 1

1Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-

Schwenningen, Deutschland

2Institut für Pathologie, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen,

Deutschland

3Institut fürPathologie, Universitätsklinikum Würzburg, Würzburg, Deutschland

4Institut für Radiologie und Nuklearmedizin, Schwarzwald-Baar-Klinikum,

Villingen-Schwenningen, Deutschland

5Klinik für Allgemein- und Viszeralchirurgie, Schwarzwald-Baar-Klinikum,

Villingen-Schwenningen, Deutschland

6Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland

Purpose: Acquired hemophagocytic lymphohistiocytosis (HLH) is a

complicating syndrome in cancer patients. HLH may be a paraneoplastic

syndrome of de novo malignancy or a complication triggered by an in-

fection in an immunocompromised patient. Two case reports illustrating

diverse roots of HLH-origin are presented.

Methods: Case report

Results: 1) A 78 y/o male patient with chronic myelomonocytic leukemia

(CMML-1) was treated with 5-azacytidine over 6 months. Aer RSV-pneu-

monia in January 2019, re-admission 4 weeks later due to aggravated dys-

pnea, renal failure and fever of unknown origin was required. Based on

clinical and laboratory fulllment of 5 out of 8 HLH-2004 criteria, the diag-

nosis of acquired HLH secondary to RSV-pneumonia was conrmed. Com-

bined HLH- and CMML treatment with corticosteroids (dexamethasone)

to suppress the cytokine storm and hydroxycarbamid to control leukemic

proliferation reversed pulmonary and renal failure and allowed discharge.

2) A 53 y/o male double organ transplant patient under long-term im-

munosuppression presented with hyperferritinemic (39.404 ng/ml) fever,

pancytopenia, splenomegaly, coagulopathy, hypertriglyceridemia (536

mg/dl), high sIL2R (4.958 U/ml) and bone marrow hemophagocytosis

fullling HLH diagnostic criteria. Nodal status and viral replication test-

ing were unrevealing. PET-CT indicated dim splenic hypermetabolic ac-

tivity. HLH-directed treatment stabilized the patient to allow diagnostic

splenectomy. Splenic T-cell lymphoma was found and T-NHL-directed

treatment was initiated.

Conclusions: Acquired HLH may indicate hidden malignancy mandating

intense diagnostic studies and interventions to detect malignancy. On the

other hand, cancer patients are at increased risk to develop acquired HLH

aer infectious complications. Individual treatment tailoring adapted to

various trigger conditions are required1.

Reference:

1. La Rosée et al., Recommendations for the management of hemophagocytic

lymphohistiocytosis in adults, Blood 2019

Disclosure Statement: e authors declare no COI.

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2018

Molecular Pathology

Poster

298

The Expression of Genetic Variants of Cytochrome CYP2C9*2

and CYP2C9*3 and their Association with Increased Risk of

Lung Cancer

Darko Katalinic 1; Ivan Aleric 1; Aleksandar Vcev 1; Stephan Bildat 2;

Lilly Soerensen 3

1Faculty of Dental Medicine and Health and Faculty of Medicine, Josip Juraj

Strossmayer University of Osijek, Department of Clinical Medicine, Department

of Internal Medicine, Osijek, Kroatien

2Herford Clinic, Teaching Hospital of the Ruhr-University Bochum, Department

of Hematology and Medical Oncology, Herford, Deutschland

3Department of Cancer Medicine, Divison of Molecular Cancer, Oslo, Norwegen

Purpose: e cytochrome P450 superfamily metabolic enzymes (P450)

could have a possible role in lung cancer susceptibility. erefore, it is im-

portant to dene the overexpression prole of P450 and to establish their

prognostic signicance in subjects with lung cancer. e aim of this study

was to investigate the possible connection among the risk of lung cancer

and frequency of genetic variants of cytochrome CYP2C9 (CYP2C9*2

and CYP2C9*3).

Methods: e study was performed among 359 patients (69% males and

31% females; mean age of 59.96 ± 18.24 years) with diagnosis of stage IV

small-cell (24.6% of patients) and non-small cell lung cancer (75.4% of

patients) compared to 167 healthy subjects (72% males and 28% females;

mean age of 69.96 ± 11.74 years). e distribution of CYP2C9 genetic

variants CYP2C9*2 and CYP2C9*3 was detected using the quantitative re-

al-time polymerase chain reaction (qRT-PCR) restriction fragment length

polymorphism (RFLP) assay. e study was conducted according to the

Declaration of Helsinki, the protocol was reviewed and approved by the

institutional Ethics committee and all patients provided written informed

consent.

Results: No statistically signicant dierences in the distribution of ge-

netic allelic variants CYP2C9*2 and CYP2C9*3 were found among the

patients with lung cancer compared to healthy subjects (p=0.648). e

CYP2C9*2 and CYP2C9*3 genetic variants were expressed at the similar

frequency in cancer and healthy bronchial tissue.

Conclusions: Our data indicate that there is no statistical signicance be-

tween the occurrence of the frequencies of genetic alleles CYP2C9*2 and

CYP2C9*3 and the increased risk of lung cancer.

References:

1. Pratt VM et al. J Mol Diagn.2019 Sep;21(5):746-755.

2. London SJ et al. Pharmacogenetics.1996 Dec;6(6):527-33.

Disclosure Statement: No conicts of interest to declare.

317

Maldi-IMAGiNG - a Tool for Proteomic Characterization

of Tumor Cells

Franziska Homann 1; Daniela Pelzel 1; Günther Ernst 1; Thomas Krüger 2;

Olaf Kniemeyer 2; Ferdinand von Eggeling 1, 3; Orlando Guntinas-Lichius 1

1Department of Otolaryngology, Jena University Hospital, Jena, Deutschland

2Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll

Institute (HKI), Jena, Deutschland

3Jena Biophotonic and Imaging Laboratory (JBIL), Jena, Deutschland

Purpose: Matrix assisted laser desorption/ionization (MALDI) imaging is

a recently developed molecular imaging method. It simultaneously reveals

the label-free detection of numerous molecules in-vitro. In this study, the

method is used in an exemplary way to obtain molecular characteriza-

tion of oropharyngeal cancer tissue and ne-needle aspiration cytology

(FNAC).

Methods: From 20 patients with SCC located in the oropharynx, both

FNAC and tissue samples from the primary tumor zone as well as from

the adjacent normal tissue zones were used. Tissue sections and cell as-

pirates were placed on glass slides. Aer sample specic processing the

sections and the cells were analyzed with MALDI imaging. Aerwards

the MALDI data were compared with histological and cytological stain-

ing. Identication of potential tumor marker was carried out with liquid

chromatography-mass spectrometry (LC-MS/MS).

Results: e assessment of the MALDI data of the tissues resulted in pro-

teomic signatures specic to SCC allowing a clear dierentiation between

malign and benign tissue areas. Dierent, already established as well as

new potential marker proteins could identied. e transfer of these data

onto the aspirates leads to new approaches in the diagnostic of FNAC.

Conclusions: MALDI imaging is an appropriate tool for the comprehen-

sive molecular characterization of tumor tissue and tumor cells of the

head and neck area. e signatures can contribute to improved diagnos-

tics of oropharyngeal carcinoma. In combination with further examina-

tions, they can provide valuable information regarding the inhomoge-

neous therapy response and contribute to a better understanding of the

tumor biology.

Reference:

1. Homann, F. et al. Laryngo-Rhino-Otol 2019; 98(S 02): S72; DOI: 10.1055/s-

0039-1686001.

Disclosure Statement: Franziska Homann has no relevant nancial or nonnan-

cial relationships to disclose.

731

Encyclopedic Tumor Analysis Guided Personalized

Treatments: a Paradigm Shift in Clinical Management

of Advanced Refractory Cancers

Dadasaheb Akolkar 1; Vineet Datta 1; Darshana Patil 1; Ajay Srinivasan 1;

Stefan Schuster 2; Rajan Datar 1

1Datar Cancer Genetics Limited, Nashik, India

2Datar Cancer Genetics Europe GmbH, Eckersdorf, Deutschland

Purpose: Standard of Care therapies have limited ecacy in advanced

refractory solid organ malignancies. Also benets from Checkpoint In-

hibitors are restricted to populations with qualifying molecular features.

We assumed that molecular and cellular investigations (‘Encyclopedic Tu-

mor Analysis’, ETA) can reveal unexplored features and target them using

combinations of cytotoxic, targeted and endocrine agents. We report the

results of the pan-cancer RESILIENT trial, where patients with advanced

refractory malignancies received ETA-guided treatments.

Methods: Fresh tumor tissue was obtained from 200 patients and used for

ETA, which included molecular proling (MP: gene alterations/expres-

sion), immunohistochemistry (IHC), and in vitro chemoresistance and

response (CRR) proling against approved anti-tumor agents. MP, IHC

and CRR datasets were integrated to generate patient specic drug priori-

ty lists with projected ecacy and safety. Patients received individualized

combinations, and treatment response was evaluated by FDG PET-CT to

determine Objective Response Rate (ORR), Disease Control Rate (DCR)

and Progression Free Survival (PFS).

Results: Among the 143 patients who received ETA-guided treatments,

126 were evaluable for response per protocol. PR was observed in 54 pa-

tients (ORR = 42.9%) and 114 patients continued to exhibit PR or SD at

study termination (DCR = 90.5%). Median PFS was 134 days. Median

PFS rate at 90 day was 93.9%. No signicant therapy related adverse events

were observed. Most patients reported stable to improved Quality of Life.

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Conclusions: Eta-guided treatments oered meaningful pan-cancer Orr

and Pfs benets in this heavily pretreated population and thus outper-

formed other systemic treatment options incl. Checkpoint Inhibitors.

735

Characterisation of Clonal and Subclonal Allelic Imbalance at

The Hla Locus in a 31 Patient Multi-Region Proled Primary /

Metastasis Clear Cell Renal Cell Carcinoma Cohort

Faiz Jabbar

Francis Crick Institute, London, United Kingdom

Purpose: Metastasis is the primary cause of death in cancer. Large-scale

studies of metastatic disease have not included analysis of matched pri-

mary tumours, which are required to distinguish tumour clones with and

without metastatic potential. Although the treatment of primary tumours

has become more successful, 5 year survival rates for metastatic renal can-

cer remain at 8%. An improved understanding of the genetic dierences

between primary and metastatic tumours could reveal distinct therapeu-

tic vulnerabilities between local and metastatic disease, which if exploited

could improve treatment or prevent metastasis. Immune evasion is re-

quired for tumour progression and metastasis.

We investigated whether genomic alterations causing the loss of human

leukocyte antigen (HLA) alleles would facilitate immune evasion and sub-

sequently promote proliferation and metastasis.

Methods and Results: We acquired the ability to decipher potential

modes of metastatic progression through simultaneous analysis of 418

primary and 278 metastatic biopsies from 31 renal cell carcinoma pa-

tients. Multiple regions from each tumour were biopsied giving us clonal

resolution. AI was investigated using uorescently labelled STR oligonu-

cleotides that were polymorphic within the HLA locus. We showed AIH-

LA was signicantly selected for within the metastases. e detection of

genomic alterations in tumour biopsies is confounded by inltration from

stromal DNA. erefore, we developed a novel bioinformatics tool that

puried and Characterised Allelic Imbalance in Tumours (CAIT). is

was achieved through mathematical deduction of signals originating from

stromal DNA. CAIT increased AIHLA detection, providing insights on

AIHLA’s prevalence and timing.

Conclusions: ese results suggest AIHLA could promote metastatic

progression. e characterisation of AIHLA could increase our under-

standing of drug-resistance mechanisms and inform the development of

immunotherapeutic agents targeting neoantigens.

Novel Agents/Early Clinical Trials

Poster

586

Entrectinib in Neurotropic Tropomyosin Receptor Kinase

Fusion Positive (NTRK-FP) Gastrointestinal (GI) Cancers:

Integrated Analysis of Patients (PTS) Enrolled in Three Trials

(STARTRK-2, STARTRK-1, and ALKA-372-001)

Gunnar Folprecht 1; Salvatore Siena 2, 3; George Demetri 4; Robert Doebele 5;

Young Kwang Chae 6; Paul Conkling 7; Ignacio Garrido-Laguna 8;

Pilar Garrido 9; Christian Rolfo 10; Darren Sigal 11; Xinhui Huang 12;

Brian Simmons 12; Chenglin Ye 12; Fortunato Ciardiello 13

1University Hospital Carl Gustav Carus, University Cancer Center UCC/NCT,

Medical Dept I, Dresden, Deutschland

2Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan,

Italien

3Università degli Studi di Milano, Department of Oncology and Hemato-

Oncology, Milan, Italien

4Dana-Farber Cancer Institute, Boston, MA, United States

5University of Colorado, Aurora, CO, United States

6Northwestern University, Chicago, IL, United States

7US Oncology Research, Virginia Oncology Associates, Norfolk, VA, United States

8University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, United States

9Ramón y Cajal University Hospital, Madrid, Spanien

10Maryland University, Greenebaum Comprehensive Cancer Center, Baltimore,

MD, United States

11Scripps Clinic, La Jolla, CA, United States

12Genentech, Inc., South San Francisco, CA, United States

13Università della Campania L. Vanvitelli, Dipartimento di Medicina di Precisione,

Napoli, Italien

Purpose: NTRK1/2/3 gene fusions cause expression of chimeric TRK

proteins with constitutively activated kinase activity, leading to oncogenic

potential across several histopathologies. Entrectinib is a CNS-active, po-

tent TRKA/B/C and ROS1 inhibitor. We present integrated ecacy and

safety data from phase 1/2 trials for entrectinib in NTRK-fp solid tumors,

focusing on pts with GI cancers.

Methods: Pts with locally advanced/metastatic NTRK-fp solid tumors

(± baseline CNS disease) conrmed by nucleic acid-based methods

were enrolled in global (>150 sites, 15 countries) trials (ALKA-372-001

[EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2

[NCT02568267]). Tumor assessments were by blinded independent cen-

tral review (BICR) using RECIST v1.1. Primary endpoints (BICR): ob-

jective response rate (ORR), duration of response (DOR). Key secondary

endpoints: progression-free survival (PFS), overall survival (OS), safety.

Results: In the total ecacy-evaluable NTRK-fp population (n=54; 10 tu-

mor types), ORR (BICR) was 57.4% (95% CI 43.2–70.8), with 4 complete

responses (7.4%). Responses occurred in all tumor types. Median (95%

CI) DOR, PFS, OS were 10.4 (7.1–NR), 11.2 (8.0–14.9), 20.9 (14.9–NR)

months, respectively. In the cohort of 8 pts with NTRK-fp GI cancers, re-

sponses by BICR were observed in 1/4 colorectal, 2/3 pancreatic, and 1/1

cholangiocarcinoma pts; all were partial. Investigator-assessed respons-

es in this GI cohort were seen in 2 colorectal and 1 pancreatic pt, and 1

cholangiocarcinoma pt. In the safety population (n=68 pts with NTRK-fp

solid tumors who received ≥1 entrectinib dose), 47% had grade 1/2 treat-

ment-related AEs (TRAEs), 38% had grade 3, 4% had grade 4; there were

no grade 5 TRAEs. TRAEs led to dose reductions in 39.7%, interruptions

in 30.9%, and discontinuations in 4.4% of pts.

Conclusions: Entrectinib was well tolerated and induced clinically mean-

ingful, durable responses in pts with NTRK-fp solid tumors, including pts

with a variety of dierent GI cancers.

Conicts of Interest:

Gunnar Folprecht: Honoraria (self) from Merck, Roche, Sano-Aventis, Bayer,

Mundipharma, Bms, MSD, Servier; Advisory/Consultancy for Merck, Roche,

Sano-Aventis, Bayer, Mundipharma, BMS, MSD, Servier; Research grant /

Funding (institution) from Merck.

Salvatore Siena: Advisory board member for Amgen, Bayer, BMS, CheckmAb,

Celgene, Clovis Oncology, DaiichiSankyo, Incyte, Merck, Novartis, Roche-Genen-

tech, and Seattle Genetics.

George Demetri: Grants, personal fees, non-nancial support, and travel support

for consulting meetings from Novartis, Bayer, Roche, Epizyme and Daiichi-San-

kyo; Grants, personal fees, and travel support for consulting meetings from Pzer;

Personal fees and travel support for consulting meetings from EMD-Serono;

Personal fees from Sano; Grants and personal fees from Ignyta; Grants, personal

fees, and travel support for consulting meetings from Loxo Oncology; Grants,

personal fees, and non-nancial support from AbbVie; Personal fees and travel

support for consulting meetings from Mirati erapeutics; Personal fees and

travel support for consulting meetings from WIRB Copernicus Group; Personal

fees from ZioPharm; Personal fees from Polaris Pharmaceuticals; Personal fees

and travel support for consulting meetings from M.J. Hennessy/OncLive; Grants,

personal fees, and travel support for consulting meetings from Adaptimmune;

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Grants from GlaxoSmithKline; Personal fees, minor equity, and travel support

to Board meetings from Blueprint Medicines, where he serves as a member of

the Board of Directors; Personal fees and minor equity options from Merrimack

Pharmaceuticals, where he serves as a member of the Board of Directors; Personal

fees and minor equity from G1 erapeutics; Personal fees, minor equity options,

and travel support to consulting meetings from Caris Life Sciences; Minor equity

options from Bessor Pharma; Minor equity options from Erasca Pharmaceuticals;

Personal fees and travel support to consulting meetings from Champions Oncol-

ogy; Grants and personal fees from Janssen; Grants, personal fees, travel support

for consulting meetings and non-nancial support from PharmaMar; Use of patent

on imatinib for GIST, licensed to Novartis with royalties paid to the Dana-Farber

Cancer Institute.

Robert Doebele: Honoraria from Genentech/Roche, Takeda/Millenium; Advi-

sory board for Genentech/Roche, Rain erapeutics; Travel reimbursement for

Genentech/Roche, Ignyta; Licensing fees for biological materials from Genentech/

Roche, Ignyta, Foundation Medicine, Loxo Oncology; Consulting for Ignyta, Loxo

Oncology, Bayer, Rain erapeutics; Sponsored research from Ignyta, Loxo Oncol-

ogy; Stock ownership at Rain erapeutics; Licensing fees from patent from Rain

erapeutics and Abbott Molecular.

Young Kwang Chae: Research grants from AbbVie, BMS, Biodesix, Lexent Bio,

and Freenome; Honoraria from Roche/Genentech, AstraZeneca, Foundation

Medicine, Counsyl, NeoGenomics, Guardant Health, Boehringer Ingelheim,

Biodesix, ImmuneOncia, Lilly Oncology, Merck, and Takeda.

Paul Conkling: Research funding from Roche, BMS, and US Oncology Research.

Ignacio Garrido-Laguna: Ad-hoc scientic advisory boards for Array, Ignyta,

Glycyx; Financial support to the Huntsman Cancer Institute from Agios, Bayer,

BMS, Eli Lilly, Halozyme, Incyte, MedImmune, Novartis, OncoMed, Pzer, Taiho

Pharmaceutical, RedHill Biopharma, Glenmark, GSK, NewLink Genetics, ARMO

Biosciences, Amgen, and Rafael Pharmaceuticals.

Pilar Garrido: Consulting and advisory services (self) from Roche, MSD, BMS,

Boehringer Ingelheim, Pzer, AbbVie, Guardant Health, Novartis, Eli Lilly,

AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaking, pub-

lic presentations (self) from Takeda, AstraZeneca, Roche, MSD, BMS, Pzer,

Novartis, Boehringer Ingelheim, Gilead, Rovi; Financial support for clinical trials

(institution) from Roche, MSD, BMS, Takeda, Lilly, Pzer, Novartis, Pharmamar,

Celgene, Sano, GSK, eradex Oncology, Blueprint Medicines; Financial support

for contracted research (institution) from Guardant Health and Sysmex.

Christian Rolfo: Speaker fees from MSD and GuardantHealth; Scientic advisor

for Mylan; Institutional research collaboration with Biomark, Inc.; Non-remuner-

ated collaboration with OncoDNA; Steering scientic committee for Oncopass.

Darren Sigal: Speakers Bureau for Celgene, Bayer; Scientic Advisory Board for

Celularity, Molecular Stethoscope, CureMatch; Patent on using TRK inhibitors to

treat neuroendocrine tumor.

Xinhui Huang: Employment at Genentech, Inc.; Stock ownership at Roche.

Brian Simmons: Employment at Genentech, Inc.; Stock ownership at Roche.

Chenglin Ye: Employment at Genentech, Inc.; Stock ownership at Roche.

Fortunato Ciardiello: Honoraria or consultation fees for speaker, consultancy or

advisory roles from Amgen, Bayer, Bristol-Myers Squibb, Celgene, Merck Serono,

Pzer, Pierre Fabre, Roche, Servier; Direct research funding as the principal inves-

tigator for institutional research projects from

Amgen, Bayer, Merck KGaA, Pierre Fabre, Roche, Ipsen; Institutional nancial

interests, nancial support for clinical trials or contracted research from Merck

KGaA, Roche, Symphogen, Array, Servier, AstraZeneca, and MSD.

All authors: Medical writing and editorial support for the original abstract was

provided by Gardiner-Caldwell Communications, Asheld Healthcare Commu-

nications and sponsored by Roche in accordance with Good Publication Practice

guidelines. Support for third-party editing assistance for this abstract, furnished

by John Carron, PhD, Sammi Cham, BA, and Niamh Gould, BA, of Health Interac-

tions, was provided by Roche Pharma AG. is study was funded by F. Homann

La-Roche, Basel, Switzerland.

766

Identication of Novel HDAC-Inhibitors Targeting Epigenetic

Dysregulations in MDAMB231 Cell Dierentiation

Knud Esser 1; Andrea Kulik 1; Dieter Niederacher 1; Hans Neubauer 1;

Thomas Kurz 2; Tanja Fehm 1

1Heinrich-Heine-University of Düsseldorf, Department of Obstetrics and

Gynecology, Düsseldorf, Deutschland

2Heinrich-Heine-Universität Düsseldorf, Institute of Pharmaceutical and

Medicinal Chemistry, Düsseldorf, Deutschland

Purpose: Targeting tumor specic epigenetic deregulations by activat-

ing silenced cellular dierentiation programs is a promising strategy for

tumor treatment. Epigenetic-acting agents are supposed to potently re-

duce solid cancer cell tumorigenicity and to render cells more prone to

common therapies. Histone deacetylase (HDAC) inhibitors represent one

innovative class of epigenetic drugs known to induce dierentiation in

distinct cancer cells.

Methods: We analysed an in-house library of 20 newly developed

HDAC-inhibitors by a cell-based phenotypic high-throughput screen-

ing system which allows the identication of potential epigenetic-acting

agents via the quantication of two innovative dierentiation markers.

MDA-MB-231 cells were used as in vitro model for complex epigenetic

deregulations leading to an early dierentiation arrest. Dierentiation-in-

ducing potency of the identied compounds was validated by quantifying

the expression of characterized dierentiation markers by qRT-PCR anal-

ysis and compared to clinically relevant HDAC inhibitors.

Results: Testing a databank of 20 novel HDAC inhibitors identied two

compounds as possible hit-candidates. ese compounds showed a high-

er pharmacological ecacy in vitro compared to current clinical HDAC

inhibitors.

Conclusions: We have successfully discovered two new HDAC inhibitors

inducing dierentiation in triple negative MDA-MB-231 cells. Further

studies will be performed to optimize pharmacological potency and to

investigate their potential suitability for anti-tumor drug development.

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2018

Oncological Pharmacy

Poster

198

Pharmacist in a Multidisciplinary Cancer Care Team in

Germany – Exception or Well-Established Model?

Svenja Dierkes; Annette Freidank; Roland Radziwill

Klinikum Fulda gAG

Purpose: ere is an increasing demand for better management of pa-

tients with cancer due to high numbers of newly diagnosed patients and

the increasing complexity of new chemotherapeutics. Pharmacists are

able to ensure the patient’s safety and quality of life.[1] e objective of this

study is to evaluate the current number of pharmacists embedded in a

multidisciplinary cancer care team in Germany.

Methods: A survey was conducted using a web-based questionnaire. It

addressed all clinical pharmacists in Germany who are ADKA (Federal

Association of German Clinic Pharmacists) members. It was distributed

via ADKA mailing list together with some basic information to ensure

comparability of the answers. It was pointed out that only one response

per hospital pharmacy is allowed.

Results: e ongoing study was started at 8th of August 2019. Up to now

the overall response rate is 34.7% (130 of 375 hospital pharmacies[2]).

Pharmacists are involved in the management of clinical studies (66.9%)

and supportive care (42.3%), as well as in establishing chemothera-

py schemes (66.9%). Although 90.8% of all participants are preparing

ready-to-administer cytostatics, only 15.4% are on ward routinely. Even

less (four pharmacists) are implemented ve days per week for at least

four hours at an oncology ward. Only two (of these four) are involved in

the entire patient care process from admission to discharge counselling

patients ensuring medication safety.

Conclusions: Although the positive impact of a ward pharmacist was re-

ported by some hospitals abroad and clinicians recommend pharmacist’s

support, the implementation in Germany is still insucient. erefore, we

encourage every clinician to consider a close cooperation with pharma-

cists to improve safe medical treatment.

References:

1. E. M Segal, et al. J Oncol Pharm Pract 2019

2. GBE-Bund.de (Accessed 18th august 2019)

Disclosure Statement: S.D., A.F., and R.R. declare no conict of interest.

567

Medication Safety in Patients Treated with New Oral

Antitumor Agents: A Prospective, Randomized Investigation

on the Impact of Intensied Clinical Pharmaceutical/Clinical

Pharmacological Care on Patient Safety and Well-Being

(AMBORA). Supported by the German Cancer Aid (70112447)

within the Comprehensive Cancer Center Erlangen-EMN

Katja Schlichtig 1; Pauline Dürr 2; Martin F. Fromm 1; Frank Dörje 2

1Friedrich-Alexander-Universität Erlangen-Nürnberg, Institute of Experimental

and Clinical Pharmacology and Toxicology, Erlangen, Deutschland

2University Hospital Erlangen, Pharmacy Department, Erlangen, Deutschland

Purpose: e increasing use of oral anticancer drugs leads to a higher re-

sponsibility for the patient and requires close management to handle Drug

related problems and non-adherence. e main objective of this study is

to investigate the eect of an intensied clinical pharmaceutical/ pharma-

cological care on medication safety and treatment satisfaction in patients

treated with new oral anticancer drugs.

Methods: 200 patients will be randomized to receive either standard

clinical care or intensive care over 12 weeks. A structured clinical phar-

maceutical/pharmacological care program including patient counseling,

medication reconciliation, and side eect management was established.

Primary outcome parameters are the number of drug related problems

(DRP) regarding the oral anticancer drug and patient treatment satisfac-

tion. Further outcome parameters are for example the number of serious

side eects, hospitalization and treatment discontinuation rates.

Results: ese are the results of an interim analysis of 129 patients.

Patients` satisfaction with anticancer treatment is signicantly higher in

the intervention group (TSQM questionnaire 92 vs. 78, p<0.001). e

number of DRP in the control group was higher than in the intervention

group (7.9 vs. 6.8 DRP per patient, n.s.). In particular, serious side eects

were signicantly reduced in the intervention group (1.3 vs. 0.7 side ef-

fects per patient; p<0.05). Rates of hospitalization and discontinuation of

anticancer treatment due to toxicity were higher in the control group (12

vs. 2 hospitalizations; p<0.01, 9 vs. 4 discontinuations; ns).

Conclusions: e data of this interim analysis show that an intensive clin-

ical pharmaceutical /pharmacological counseling can reduce the number

of drug related problems associated with new oral anticancer drugs. e

early intervention reduced serious side eects as well as therapy discon-

tinuation and hospitalization rates due to toxicity. Patients´ satisfaction

was signicantly higher.

Disclosure Statement: e authors have no conicts of interest to disclose.

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Pediatric Cancer

Poster

396

Impairments in Cardiovascular Health and Physical Activity

Early after Treatment for Pediatric Cancer

Sabine Kesting 1, 2; Dominik Gaser 1, 2; Tina Keiser 3; Christiane Peters 2;

Renate Oberhoer 2; Irene von Luettichau 1

1Kinderklinik München Schwabing, TUM School of Medicine, Department

of Pediatrics and Children’s Cancer Research Center, Technical University of

Munich, Munich, Germany

2Institute of Preventive Pediatrics, Department of Sport and Health Sciences,

Technical University of Munich, Munich, Germany

3Department of Sports Medicine and Exercise, Justus-Liebig University Gießen,

Gießen, Germany

Purpose: Cardiovascular diseases in pediatric cancer survivors are known

late sequelae1. Cardiovascular health is usually related to physical activi-

ty (PA). Reduced PA during cancer treatment results in impaired motor

performance2. erefore, reintegration into sports structures might be

aected.

Methods: Participants (6-18 yrs, mixed entities) were recruited during

follow-up care from April to June 2019. Peripheral and central systolic/di-

astolic blood pressure (pSBP/pDBP/cSBP) and pulse wave velocity (PWV)

were assessed using the Mobil-O-Graph®. e MOON test scaled motor

performance. PA aspects were quantied with the KiGGS study question-

naire. All data was compared to reference values.

Results: 40 children (11.3±3.8 yrs, 50% ♀) were recruited 1.6±1.8 years

post-treatment. PSBP (z-score 0.9±1.7, p = 0.003), pDBP (0.8±1.9,

p = 0.033) as well as cSBP (≥8 yrs: 0.6±1.3, p = 0.011) were signicantly in-

creased compared to reference values. PWV was elevated (<8 yrs: 1.2±2.9,

p = 0.374; ≥8 yrs: 0.6±1.9, p = 0.127). Motor performance was reduced in

nearly all dimensions. 17% reported 60 min of daily PA as recommended

by the WHO. 50% were active sports club members, but 1/3 did not re-

sume their former membership.

Conclusions: Early aer treatment, children show increased blood pres-

sure, a risk factor for cardiovascular diseases. Impaired motor perfor-

mance and low PA underline the support needed regarding engagement

in PA to potentially counteract risk factors and improve cardiovascular

health. Implementation of sports oers during and aer treatment should

be considered as a meaningful, cost-eective preventive approach in

terms of late eects associated with physical inactivity.

References:

1. Hudson M et al. Clinical Ascertainment of Health Outcomes Among Adults

Treated for Childhood Cancer, JAMA 209; 2013:2372-81.

2. Ness KK et al. Limitations on physical performance and daily activities among

long-term survivors of childhood cancer. Am Intern Med 14; 2006:639-47.

502

Short and Long Term Outcome for Patients with Surgical

Removal of Sacrococcygeal Teratoma in Newborns and

Infancy

Maria Ai 1; Vera Schellerer 2; Manuel Besendörfer 2

1Uniklinik Erlangen, Kinderklinik, Erlangen, Deutschland

2Uniklinik Erlangen, Kinderchirurgie, Erlangen, Deutschland

Purpose: is study evaluates the short and long term outcomes of new-

born and infant cases with sacrococcygeal teratoma removal. We exam-

ined the physical and neurological impairment aecting these patients.

Methods: A total of 21 patients underwent surgical procedure between

July 2001 and July 2019 in our pediatric surgery department. We gathered

information from the patient medical records, postoperative medical in-

terviews, and performed physical examinations. We used this information

to evaluate the status and the extent of the impairment of the patients. e

patients received follow up treatment in according to the MAKEI recom-

mendations for duration of 10 years.

Results: 21 patients had surgical procedure through our department due

to sacrococcygeal teratoma (male: n = 5, female n = 16). SCT are more

common in females with a 3 to 4:1 ratio. Pre-operative assessment in-

cluded prenatal ultrasound (n = 20), prenatal MRI (n = 7), neonatal MRI

(n = 10). e distribution of our Altman classication was: 14% Altman I

(n = 3), 57% Altman II (n = 12), 10% Altman III (n = 2), 10% Altman IV

(n = 2), 10% Altman unknown (n = 2). e surgery was performed at the

age of diagnosis which was on average the 3nd day of life (range: 0 to 13

day of life). e weight median was by 2800g with a range of 2570 g. Out

of the 21 patients, 12 tumors were completely removed with R0 surgical

resection (n = 12), 3 tumors with R1 (n = 3) and 6 tumors with RX (n = 6)

surgical resections. Histological ndings included predominantly chon-

droid (n = 12) and neuroectodermal (n = 10) parts. e maturity level

was evaluated: 33% GC 0 (n = 7), 24% GC 1 (n = 5), 14% GC 2 (n = 3),

5% GC 3 (n = 1), 14% GC unknown (n = 6). Post-operative complications

included surgical site infections (n = 6), bowel perforation (n = 1), and

post-operative mortality (n = 2).

Conclusions: Sacrococcygeal teratoma is a heterogeneous entity of the

germline tumors and the prognosis is signicantly better for patients who

had R0 surgical resection and low GC scores. Postoperative and long term

complications are tolerable. Follow ups are necessary to determine future

reoccurrence of the tumor.

625

A Comprehensive Map of Genetic Vulnerabilities in ATRT

Subgroups

Daniel Merk 1; Sophie Hirsch 1; Cristiana Roggia 2; Federica Piccioni 3;

Michael Spohn 4, 5; Ulrich Schüller 5, 6; Ghazaleh Tabatabai 1

1Interdisciplinary Division of Neuro-Oncology, Departments of Neurology

& Stroke and Neurosurgery, Laboratory of Clinical and Experimental Neuro-

Oncology, Hertie-Institute for Clinical Brain Research, University Hospital

Tübingen, Eberhard Karls University Tübingen, Tübingen, Deutschland

2Institute of Medical Genetics and Applied Genomics, University Hospital of

Tübingen, Eberhard Karls University Tübingen, Tübingen, Deutschland

3Broad Institute of MIT and Harvard, Cambridge, United States

4Bioinformatics Core, University Medical Center Hamburg-Eppendorf ,

Hamburg, Hamburg, Deutschland

5Research Institute Children`s Cancer Center Hamburg, Hamburg, Deutschland

6Department of Pediatric Hematology and Oncology, University Medical Center

Hamburg-Eppendorf , Hamburg, Hamburg, Deutschland

Purpose: Brain tumors are the leading cause of cancer-related deaths in

children and adolescents. Embryonal brain tumors are a group of high-

grade neoplasms which primarily aect young patients, and atypical

teratoid rhabdoid tumors (ATRTs) are the second most common type

of tumor within this group. In spite of intensive research eorts and the

knowledge of molecular mechanisms driving subgroup-specic heteroge-

neity within ATRTs, survival estimates stay relatively low as compared to

other tumor entities with a median survival of around 17 months. More

ecacious and durable therapies are urgently needed to improve the sit-

uation of patients.

Methods: We investigated genetic, epigenetic, and transcriptional features

of seven distinct human ATRT cancer cell lines in order to assign those

cell lines to three molecular subgroups described for ATRTs. Subsequent-

ly, we will perform genome-wide CRISPR/Cas9 knockout screens for

these ATRT cell lines in order to identify genetic vulnerabilities and novel

therapeutic targets for this tumor entity.

Results: Detailed analyses including mRNA expression- and DNA meth-

ylation-based prediction approaches provide evidence that our selection

of ATRT cell lines (BT12, BT16, CHLA02, CHLA04, CHLA05, CHLA06,

CHLA266) recapitulates features of all three molecular subgroups of

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ATRT, namely ATRT-TYR, ATRT-SHH, and ATRT-MYC. Dependen-

cies discovered in the rst screen using BT12 cells were highly enriched

for fundamental cellular processes such as transcription and translation,

thereby validating our approach. We identify 190 BT12-specic cell es-

sential genes, including 44 genes in potentially druggable categories and

seven genes representing clinically actionable targets. We are preparing to

screen additional ATRT cell lines of all molecular subgroups in order to

establish a comprehensive overview of ATRT vulnerabilities.

Conclusions: Our data will provide a comprehensive map of dependen-

cies for distinct ATRT subgroups which will serve as a starting point in the

development of targeted therapies for this tumor entity.

682

Feasibility of Indoor-Wall Climbing with Pediatric Cancer

Survivors

Vivien Lösse1, Aram Prokop2, Sarah Otten1, Eva Schmidt1, Benjamin

Kröger1, Volker Maas2, Wilhelm Bloch3, Julia Däggelmann1

1Institut für Kreislauorschung und Sportmedizin Abt. molekulare und zelluläre

Sportmedizin, Deutsche Sporthochschule Köln, Köln, Deutschland,

2Kinderkrankenhaus Amsterdamer Straße, Köln,

3Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule

Köln

Purpose: To assess feasibility of an indoor-wall climbing intervention for

pediatric cancer survivors.

Methods: Eight pediatric cancer survivors (6.50 – 20.67 years, mixed di-

agnoses) (patient group, PG) and ve healthy controls (7.42 – 20.67 years)

(healthy group, HG) participated in an indoor-wall climbing intervention

for 8-9 weeks. Supervised training was oered once a week for 60 min.

Feasibility was assessed by adverse events leading to study drop-out. Addi-

tionally, side eects like temporary muscle pain/ injuries and compliance

were evaluated. An evaluation questionnaire was used to determine train-

ing acceptance by participants and parents.

Results: No adverse events or side eects were documented. Only one

child reported that the climbing intervention was too exhausting due to

insucient breaks. Participants completed an average of 56,78% (25% –

100%) of the oered training sessions. Reasons for non-participation were

reported in 28 cases which were lack of time (80%) and medical issues like

infections (20%). Overall, 13 children (PG and HG) and 9 parents (PG

and HG) completed the questionnaire. Children generally liked the climb-

ing intervention and stated to feel stronger and more condent. ey were

interested in continuing indoor wall-climbing.

Conclusions: Indoor-wall climbing with pediatric cancer survivors is fea-

sible and well-accepted. Study results encourage to assess potential eects

of indoor-wall climbing in pediatric oncology.

Disclosure Statement: e authors declare nothing to disclose.

818

Secondary Malignancies following Ewing Sarcoma Treatment

Isabelle Kaiser

Kinderheilkunde III, Universitätsklinikum Essen

Purpose: Ewing Sarcoma (EwS) is an aggressive, bone- and so tissue

sarcoma found in children, adolescents and young adults. Due to intense

multimodal therapy, survival rates have increased to 75% in patients with

localized disease1. Consequently, long-term surveillance of late eects

has gained importance. We investigated secondary malignant neoplasms

(SMNs) following EwS-treatment. is study investigated relative risk and

prognostic factors of SMN development and compared dierent SMN risk

characteristics. Time of latency between EwS and SMN diagnosis was also

examined.

Methods: e following GPOH studies supplied data: CESS 86, CESS 91P,

EICESS 92 and Euro-Ewing 99; data from a total of 3097 patients were

included. Time to SMN occurrence and survival rates aer EwS diagnosis

were analyzed. Cumulative incidences and Odds ratios for cause-specic

risks were computed.

Results: Median age of EwS diagnosis was 16 years (2–68 years). Notably,

35% had been diagnosed with metastatic EwS. Metastases were localized

mainly in the lung, bone marrow and other bones. A total of 75 patients

(54% female, 46% male) with 76 SMNs were identied. Two patients

developed two dierent SMNs. SMNs manifested as hematological neo-

plasms (42%) and solid tumors (58%) at a mean latency time of 7.8 years

following primary EwS diagnosis. In total, 58/74 (78%) patients received

radiation treatment. Twelve out of 15 (80%) observed Osteosarcomas

were localized within a previously irradiated eld.

Conclusions: Ewing Sarcoma survivors are at risk of developing SMNs. In

particular, hematological neoplasms (AML and MDS), as well as Osteo-

sarcomas were recorded following EwS treatment.

Reference:

1. Grünewald T., Cidre-Aranaz F., Surdez D. et al. (2018). Ewing sarcoma. Nature

Reviews. Disease Primers 4(5). doi: 10.1038/s41572-018-0003-x

Palliative Care

Poster

Parental Dealing with Diuse Intrinsic Pontine Glioma in

Children

Kalinka Radlanski 1; Maite Hartwig 2; Uwe Kordes 1

1Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische

Hämatologie und Onkologie, Hamburg, Deutschland

2KinderPaCT - Hamburg e.V., Hamburg, Deutschland

Purpose: Diuse intrinsic pontine glioma (DIPG) in children is a dis-

mal disease with median overall survival (OS) of less than a year. Usually

palliative care is involved. Open communication about death eases dying

for children and surviving for parents. is study establishes case reports

based on parental confrontation with DIPG. During the course of DIPG

designated key points exist. We determine specic needs of parents and

children as well as typical problems in interaction between families and

care givers. e results lead to recommendations and improvements for

existing treatment concepts.

Methods: We conducted a problem-oriented guided interview followed

by a qualitative content analysis according to Mayring.

Results: 13 parents of 7 children (aged 5-16 years) were interviewed. e

children’s median OS was 8 months and 4 days. Palliative home care was

involved in 5 families. Palliative care generally met the needs of the exam-

ined families. Parents stated overall satisfaction and comfort regarding to

most subjects (management of physical symptoms and support, provision

of information, family support, patient psychological care). Communica-

tion about death is a relevant inductive category. Out of 7 children it was

assumingly spoken openly to only one child. Two families remained in

mutual pretense. Two children were actively prevented by their parents

to have open communication. In two other cases the concept remains un-

clear. All parents regret that they have not talked to their children about

death.

Conclusions: Parents are less burdened when palliative care is involved

in the treatment of their children’s DIPG. e overall load of statements

about not talking with children about their death meets the relevance of

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this topic in literature. Concepts need to be established on how to rise

attention to the chances that open communication about death oers for

both children with life-limiting diseases and their families.

Reference:

1. Radlanski K., Hartwig M., Kordes, U. (2019) Parental Dealing With Diuse

Intrinsic Pontine Glioma in Children. EAPC Abstracts, Palliat Med

Dealing with Desire to Die in Patients with Incurable Cancer:

Recommendations of the German S3 Guideline Palliative

Medicine

Raymond Voltz 1, 2, 3, 4; Kerstin Kremeike 1; Anne Pralong 1; Steen T Simon 1;

Claudia Bausewein 5; Reinhard Lindner 6

1Departement of Palliative Medicine, University of Cologne, Faculty of Medicine

and University Hospital, Cologne, Deutschland

2Center for Health Services Research (ZVFK), University of Cologne, Faculty of

Medicine and University Hospital, Cologne, Deutschland

3Center for Integrated Oncology (CIO), University of Cologne, Faculty of

Medicine and University Hospital, Cologne, Deutschland

4Center for Clinical Studies (ZKS), University of Cologne, Faculty of Medicine and

University Hospital, Cologne, Deutschland

5Department of Palliative Medicine, Ludwig-Maximilians-University Munich,

Faculty of Medicine and Munich University Hospital, München, Deutschland

6Institute of Social Work, University Kassel, Faculty of Humanities, Kassel,

Deutschland

Purpose: Desire to die (DD) is common in palliative patients. Medical

advance and improved therapy options do not cancel out DD, but on the

contrary many patients think about dying and ask about the meaning of

life. Health practitioners are oen confronted with these thoughts. e

current national and international state of knowledge and experience in

dealing with DD oers orientation and assurance in responding to it in an

appropriate manner.

Methods: Development of evidence and consensus based recommenda-

tions with the participation of more than 60 professional societies.

Medline, PsycInfo, and Cochrane Library databases were systematical-

ly searched for relevant publications on proactively addressing DD, and

selected according to dened inclusion criteria. Findings were assessed

and built the base for developing recommendations. Evidence based and

consensus based statements were consented in a formal process.

Results: e expert panel agreed on 19 statements and recommendations

dealing with DD issues such as dierential diagnosis, potential back-

ground and meaning, how to deal with DD, possible options for action

and legal framework. e handling of DD within the treatment team, pos-

sible support from external experts and the involvement of relatives are

also covered within the guideline.

Conclusions: e guideline aims to support decision-making in practice

and provides systematically developed recommendations on the basis of

the best available evidence and clinical experience of a large number of

experts. e recommendations concerning DD aim at helping with (pro-

actively) addressing potential DD as well as dealing with them. ere-

fore they should be considered a contribution to the advancement of

multi-professional competence in palliative care.

Disclosure Statement: e authors declare no conict of interest.

123

Stability of Cancer Patients´ Unmet Spiritual Needs and

Spiritual Wellbeing in Palliative Care Units

Arndt Büssing 1; Klaus Baumann 2; Jochen Rentschler 3; Gerhild Becker 4

1Professorship Quality of Life, Spirituality and Coping, Witten/Herdecke

University, Herdecke, Deutschland

2Caritas Science and Christian Social Work, Albert-Ludwig University Freiburg,

Freiburg, Deutschland

3Department Hematology / Oncology / Palliative Medicine, Ortenau-Klinikum

Oenburg-Kehl, Oenburg, Deutschland

4Chair of Palliative Medicine, Clinic for Palliative Medicine, Freiburg University

Hospital, Freiburg, Deutschland

Purpose: Duration of patients´ stay in palliative care units (PCU) is de-

creasing, and thus options to profoundly provide spiritual care. Aim was

thus to analyze patients´ unmet spiritual needs at the beginning and end

of their PCU stay.

Methods: Pre-post analysis (paired t-test) of 65 patients´ spiritual needs

(SpNQ-20), spiritual wellbeing (FACIT-Sp), life satisfaction (BMLSS), sat-

isfaction with team support (BMLSS) and perceived health status (VAS)

with standardized questionnaires in two PCUs. IRB-Approval 316/14.

Results: Patients´ primary diagnosis was cancer (99%; 62% women, mean

age was 64±11 years; 73% Christians, 2% Muslims, 24% without religious

aliation). e Meaning component of their spiritual wellbeing scored

highest (3.19±0.70), followed by Peace (2.45±0.78) and Faith (1.80±1.34).

Among unmet spiritual needs, Inner Peace needs (1.59±0.91) and Giv-

ing/Generativity needs (1.42±0.93) scored highest, Religious needs

(0.88±0.93) and Existential needs (0.72±0.83) scored rather low. Most

stayed for 2-3 weeks at the PCU (65%). Within this time frame, neither

spiritual needs nor spiritual wellbeing nor life satisfaction changed sig-

nicantly, while their perceived health status improved (M -8.7±18.6;

p<.001). Within the sample, 66% felt that their spiritual needs were sup-

ported ’very well’ by the hospital sta (which is not specically trained in

spiritual care issues), 21% stated ‘quite well’, and 13% were not satised.

Conclusions: e time frame to provide profound spiritual care support

is rather limited. Although most felt supported in terms of their spiritual

needs, neither their needs nor their wellbeing scores changed signicantly.

Nevertheless, the individual development of spiritual needs and spiritual

wellbeing might be very dierent, and thus hospital sta has to be aware

that also an ‘aggravation’ of unmet needs could be expected (indicating

either stronger awareness or increase of fear and burden).

Disclosure Statement: e authors disclose any conicts of interest.

143

Development of a Training Program to Enhance

Communication Skills Regarding Early Referral to Palliative

Care in Advanced Cancer Patients – The Palli-Kom Study

Nele Harnischfeger 1; Hilke M. Rath 2; Anne Letsch 3; Peter Thuss-Patience 4;

Bernd Alt-Epping 5; Carsten Bokemeyer 1; Corinna Bergelt 2; Karin Oechsle 1

1Palliativmedizin, 2. Medizinische Klinik und Poliklinik, Universitätsklinikum

Hamburg-Eppendorf, Hamburg, Deutschland

2Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum

Hamburg-Eppendorf, Hamburg, Deutschland

3Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und

Tumorimmunologie, Charité-Universitätsmedizin Berlin, Campus Benjamin

Franklin, Berlin, Deutschland

4Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und

Tumorimmunologie, Charité-Universitätsmedizin Berlin, Campus Virchow,

Berlin, Deutschland

5Klinik für Palliativmedizin, Universitätsmedizin Göttingen, Göttingen,

Deutschland

Purpose: To develop a communication training for physicians who treat

cancer patients to promote an early referral to palliative care in advanced

cancer patients. e training aims to strengthen the ability to address pal-

liative care related topics constructively and early during disease trajecto-

ry. e basis of the training development will be focus groups, literature

and expert discussions.

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Methods: In addition to an intensive literature search to identify relevant

training contents, we conducted four focus groups with a total of 28 physi-

cians of varied specialization and levels of experience (M age = 39.5, SD =

8.92). Discussed topics were professional and communicative competen-

cies, personal barriers and the desired training structure. e talks were

audiotaped, transcribed and analyzed via qualitative content analysis.

Results: Due to the focus groups (average length: 90 minutes) we identi-

ed numerous aspects, which the participating physicians considered to

be crucial to the training. e need for a rectication of the understanding

of palliative care including its benets was especially emphasized. Also,

knowledge about symptom control and palliative care structures seem of

particular importance. Highlighted communication skills were an adapt-

ed language, the balance between honesty and hope, and the consider-

ation of individual information needs. Crucial personal barriers are a high

emotional involvement, especially in young patients, and the diculty of

being unable to heal. Participants desire a realistic training with a high

practical part. Personal aspects like coping shall be addressed.

Conclusions: e daily experience of physicians is a valuable source to

identify necessary competencies for early integration. Physicians have

precise expectations towards a training on communicating palliative care

related topics. Results of the focus groups were supplemented by ndings

from literature search. is will now be used to specify content and didac-

tics of the training.

Disclosure Statement: e authors declare no conict of interest.

296

Full Local Control in a Giant Ulcer of Advanced Breast Cancer

by Denitive Radiotherapy Only

Kalinka Radlanski; Dipl.-Phys. Oliver Bislich; Björn Peters;

Fabian Fehlauer

Strahlenzentrum Hamburg MVZ, Hamburg, Deutschland

Purpose:Female patient, *1931 with satisfying health conditions, Kar-

nofsky index (KI) 70%. Patient is widowed with no children and lives

in her own home with the support of a local care team. She was acutely

hospitalized with delirium due to exsiccosis and a suspected mild stroke.

Accidentally a large high risk tumor of the le mamma was found (cT4

cN0 cM0, triple negative hormone receptor status, Ki67 index 90%). In-

terdisciplinary oncologic tumor conference advised surgery followed by

chemotherapy. Both declined by patient, she primarily consulted radio-

therapy. Clinical examination showed a giant ulcer of 10 x 12 x 8 cm in

upper quadrants of le breast with spontaneous bleeding, brinous slimy

coat/secretion and strong odour. Patient’s only distress was caused by ul-

ceral staining of her clothes.

Methods:Ambulatory radiotherapy (RT) of le mamma with 48 Gray

(Gy) photons in 3 Gy single fractions, ve days a week with the use of a 8

mm moulage. Wound care with Octenilin® and manual necrosis ablation.

Weekly doctor’s visits.

Results:36,0 Gy: bleeding has stopped, yellowish brinous coat. 48,0 Gy:

much more compact ndings, no spontaneous bleeding/secretion. Mod-

est erythema of treated mamma (common toxicity criteria, CTC=2), two

small epitheliolyses (CTC=0-1), no edema of mamma or arm. KI 70%.

Very satised patient. Wound care is to be continued. 1. follow-up, 3

months aer RT: mild erythema, signicantly smaller tumor. Ulcer almost

healed, 5 cm residuum with slimy coat. Mild edema of treated mamma.

Very satised patient, KI 90-100%. 2. follow-up, 7 months aer RT: intact

skin, former ulcer is fully healed. No edema. Very satised patient, KI

90-100%.

Conclusions: Denitive RT as sole treatment can be considered as a su-

cient palliative strategy to achieve local control in advanced breast cancer

with ulceration. We controlled local symptoms and reached full healing of

the ulcer. We were able to not only sustain but raise the quality of life of

a self-sucient senior in the severe health condition of advanced breast

cancer. She experiences no impairment of daily life.

333

Music at the Palliative Care Unit (PCU) – A Volunteer Project

with Young Adults

Katrin Berndt 1; Daniela Heise 1; Heike Büntzel 2; Jens Büntzel 2

1Schwimmverein Nordhausen, Nordhausen, Deutschland

2Abteilung Palliativmedizin, Südharz-Klinikum Nordhausen, Nordhausen,

Deutschland

Purpose: Music could help to vercome social isolation at palliative care

institutions. Young volunteers have combined swim sports with this social

idea.

Methods: Since 2006 the Swim Club Nordhausen 1990 is taking part in

24-h-competitions in order to fundraise the project of our PCU. e club

donated an e-piano in 2014 and from then every 2-3 month concerts

were given to our patients. Each concert has 20-30 visitors and patients

listening the young artists. In 2018 we were able to engage a professinal

guitarrist making active music together with the individual patients every

month.

Results: 167 young volunteers have taken part in the fundraising project.

26 concerts were organized presenting piano, guitar or choral music since

March 2014. 289 patients were able to take part in these concerts. More

than 600 family members were guests of the young artists. Active music

oer was used by 53 patients at 11 sessions, e.g. 40% of possible patients

have had benet from this new apporach since January 2018.

Conclusions: Palliatve patients consume music in passive as well as active

way. Its integration helps to overcome their isolation. Furthermore young

artists become embassadors of hospice ideas.

Disclosure Statement: e authors disclose any conict of interest.

574

“But you need a Questionnaire Like This”: Real Life Experience

of Quality of Life Assessment in Outpatients with Lung and

Prostate Cancers – A Longitudinal Cohort Study

Eileen Ratzel 1; Christina Gerlach 1, 2; Ina Pretzell 2; Elke Tafel-Stein 3;

Thomas Kindler 2; Martin Weber 1

1Interdisziplinäre Abteilung für Palliativmedizin, Universitätsmedizin Mainz,

Mainz, Deutschland

2Universitäres Centrum für Tumorerkrankungen, Universitätsmedizin der

Johannes Gutenberg Universität Mainz, Mainz, Deutschland

3Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsmedizin der

Johannes Gutenberg Universität Mainz, Mainz, Deutschland

Purpose: Quality of life (QoL) assessment with patient-reported outcome

measurements (PROMs) improves patients’ QoL. It is a prerequisite in the

certication process for oncology centers of the German Cancer Society

(DKG). e aim of the study was to test the feasibility of PROMs (Inte-

grated Palliative Outcome Scale IPOS, and Distress ermometer DT) in

outpatients with advanced lung and castration-resistant prostate cancer,

both diseases beyond recovery.

Methods: e process of longitudinal QoL assessment with IPOS and

NCCN-DT was observed for 15 months. Besides patients’ distress we also

analyzed the numbers of requests for supportive services as a consequence

of the patients’ ndings in the questionnaires. Focus group interviews

with patients, informal caregivers and health care professionals (HCP)

were thematically analyzed.

Results: Ninety-seven percent (n=125) out of 129 eligible patients

received a questionnaire for one time at least. However, quarterly

assessment as recommended was achieved only in 60% of prostate

cancers, and 48% of lung cancer patients. IPOS showed a high face and

content validity and both questionnaires were well accepted. Patients did

not feel uncomfortable with lling in the questionnaires. HCP found the

instruments helped to focus and structure the time for the doctor-patient-

contact. Some patients pointed out diculties with the DT in terms of

comprehension. Due to lacking process and to organizational challenges

the achieved response rates were low as were the rates of consultations

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with supportive services. Monitored hand-over of the questionnaires

improved their implementation.

Conclusions: PROMs were regarded as important by lung and prostate

cancer outpatients as well as HCP. To facilitate consequences they should

be realized as standardized intervention rather than pure assessment. e

results must be accessible in a straightforward way to gain the maximum

benet for patients and health care processes. e eects on a direct data

input into the electronic patient chart, such as results from laboratory

tests, should be tested.

Pege

Poster

Anwendung des Niedrigenergielaser (Low Level Laser LLL)

Zur Prävention und Behandlung der oralen Mukositis bei

onkologisch erkrankten Erwachsenen und Überprüfung der

Wirksamkeit – Eine prospektive Beobachtungsstudie

Rudolf Nieth

Marburg, Universitätsklinikum UKGM, Marburg, Deutschland

Zweck: Orale Mukositis (OM) ist eine der Nebenwirkungen der Trans-

plantation hämatopoetischer Stammzellen(HSCT), die zu erheblicher

Morbidität führt. Ziel dieser Studie war es, die Wirkung eines speziellen

Mundpegeprogramms mit Lasertherapie bei der Behandlung von Pati-

enten, die eine HSCT erhalten zu überprüfen.

Methoden: Bei den Patienten wurden ab dem Tag der Behandlung ein-

mal täglich beide Wangen vorbeugend von außen für maximal 5:20 Mi-

nuten mit dem Low Level Lasergerät Twin 21+ mit den Einstellungen

21x100mW, 16,0J/LD Multifrequenz bestrahlt

Ergebnisse: Die hier vorgelegte Arbeit zeigt die positive Wirkung des

Lasers für das beschriebene Patientenklientel. Die Schwere der Mukositis

nach WHO konnten über alle Schweregrade hinweg reduziert werden.

Fazit: Eine Einführung der prophylaktischen Behandlung von onkol-

ogischen Patienten mittels der Lasertherapie kann somit zugestimmt

werden. Auch eine Kostenreduktion ist zu erwarten.

Quellenangaben:

1. Oberoi, S.; et al. (2014): Eect of Prophylactic Low Level Laser erapy on

Oral Mucositis. A Systematic Review and Meta-Analysis. In: PLoS ONE 9 (9),

S. e107418.

2. Blijlevens, et al. (2008): Prospective Oral Mucositis Audit. Oral Mucositis in

Patients Receiving High-Dose Melphalan or BEAM Conditioning Chemo-

therapy--European Blood and Marrow Transplantation Mucositis Advisory

Group. In: Journal of Clinical Oncology 26 (9), S. 1519–1525.

3. Curra, M.; et al. (2018): Chemotherapy protocols and incidence of oral mucosi-

tis. An integrative review. In: Einstein (Sao Paulo, Brazil) 16 (1), eRW4007.

4. Bezinelli, L., et al. (2014): Cost-eectiveness of the introduction of specialized

oral care with laser therapy in hematopoietic stem cell transplantation. In:

Hematological oncology 32 (1), S. 31–39.

5. Lalla, R. V.; et al. (2014): MASCC/ISOO clinical practice guidelines for the

management of mucositis secondary to cancer therapy. In: Cancer 120 (10), S.

1453–1461.

Oenlegungserklärung: Die Fa. MKW Laser hat keinerlei Einuss auf die Ergeb-

nisse oder anderweitig ausgeübt

Immuntherapie: Herausforderung für Pegefachkräfte in Der

Thorax-Onkologie

Cornelia Kloft

Lungenkrebszentrum Mittelhessen, Klinik Waldhof Elgershausen, Greifenstein,

Deutschland

Zweck: In der orax-Onkologie, insbesondere beim nichtkleinzelligen

Lungenkarzinom, ndet eine rapide Entwicklung neuer erapien statt.

Diese Entwicklung stellt die onkologische Pege vor immer neue Heraus-

forderungen. Hier ist ein Wissensdezit zu verzeichnen, was die Wirk-

weise und die immunbedingten Nebenwirkungen angeht.

Methoden: Der Aufsatz erklärt die Wirkungsweise der Immunonkol-

ogie und geht auf die immunbedingten Nebenwirkungen ein. Es wird

eingegrenzt, bei welchen Entitäten in der orax-Onkologie diese era-

pieform hauptsächlich zum Einsatz kommt. In einer Reihe von Patienten-

interviews wurde beispielha der Wissensstand von einzelnen Patienten

ermittelt. Viele Informationsmaterialien, die für die Patientenedukation

zur Verfügung stehen, werden im Aufsatz verglichen. Es werden emen

für Beratungsgespräche herausgearbeitet. Um eine gute Beratungskompe-

tenz in der Pege zu gewährleisten, ist die Mitarbeiterschulung ein wich-

tiger Aspekt.

Ergebnisse: Den besten Schutz vor unerwünschten Nebenwirkungen

könnten Krebspatienten haben, wenn sie selbst Experten für ihre Behan-

dlung wären. Der Schwerpunkt in der Patientenedukation sollte daher auf

dem Beratungsgespräch liegen. Wenn Patienten Fragen haben, sind Peg-

ende häug die ersten Ansprechpartner. Deshalb spielen sie eine wichtige

Rolle als Informationsgeber. Um das Wissen der Pegenden zu erweitern,

ist die innerbetriebliche Fortbildung als fester Bestandteil der Mitarbeit-

erschulung unverzichtbar.

Fazit: Eine gelungene Immuntherapie bedeutet für unsere Patienten eine

deutlich längere Überlebenszeit bei relativ guter Lebensqualität. Das Ex-

pertenwissen von Patienten und Pegenden kann dazu einen entschei-

denden Beitrag leisten.

Umgang mit dem Fatigue-Syndrom bei Krebspatienten

Heike Hingst; Ute Stutz

Universitätsmedizin Greifswald, Patienteninformationszentrum, Greifswald,

Deutschland

Zweck: Um Aufschluss über die Einstellung zum Erscheinungsbild des

Fatigue-Syndroms zu bekommen und zu sehen, wo noch Informationsbe-

darf besteht, wurde eine Befragung durchgeführt.

Ziel der Befragung war:

– den Wissenszustand der ärztlichen und pegenden Kolleg*innen

festzustellen

– eine Fatigue-Prophylaxe auch in anderen Bereichen des onkolo-

gischen Zentrums zu etablieren

– den Wissensstand zu verbessern und Weiterbildungen gezielt

planen zu können

Methoden: Es wurde in einem Zeitraum von 4 Wochen auf 13 Stationen

erfragt, wie das Wissen über das Fatiguesyndrom selber eingeschätzt wird

und durch welche Symptome Betroene am meisten beeinträchtigt sind.

Weiterhin wurde erfragt, ob auf Zeichen eines Fatigue-Syndroms geachtet

wird und wie der weitere Umgang bei Erkennen von Symptomen erfolgt.

Ergebnisse: Es wurden 322 Bögen ausgeteilt, von denen 115 ausgefüllt

wurden. Zwischen den Stationen gibt es erhebliche Unterschiede hin-

sichtlich des Wissens über das Fatigue-Syndrom., wobei das Wissen dort

größer eingeschätzt wird, wo bereits eine Fatigue-Beratung durch das PIZ

erfolgt/e.

Insgesamt gesehen geben jedoch nur 13,1% der Antwortenden – und

zwar unabhängig von ihrer Berufserfahrung – an, sehr gutes oder gutes

Wissen zum tumorbedingten Fatigue-Syndrom zu besitzen.

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Bei der Einschätzung, wie viele Patientinnen und Patienten ein Fa-

tigue-Syndrom entwickeln, gibt es erhebliche Unterschiede in den Abtei-

lungen: Insgesamt gesehen glauben die Befragten, dass weniger als die

Häle der Patientinnen und Patienten Fatigue-Symptome zeigen. Dabei

verlassen sich die Befragten überwiegend auf die eigene Einschätzung,

Screeninginstrumente werden selten genutzt.

Insgesamt gesehen sind die Beratungsmöglichkeiten des PIZ in Bezug

auf das Fatigue-Syndrom nur bei ca. 30% aller Befragten bekannt, wobei

hier ein deutlich höherer Bekanntheitsgrad in den Kliniken vorliegt, in

denen bereits eine Beratung erfolgt.

Fazit: Der Wissenstand zum ema Fatigue muss ausgebaut werden.

Quellenangaben:

1. FIBS- Fatigue individuell bewältigen

250

Die Rolle von Krebserkrankungen bei der Langzeitpege

durch Angehörige

Katharina Gramann-Weschke 1, 2; Annegret Paelecke 2

1Fakultät für Gesundheitswissenschaften, gemeinsame Fakultät der

Brandenburgischen Technischen Universität Cottbus - Senftenberg, der

Medizinischen Hochschule Brandenburg Theodor Fontane und der Universität

Potsdam

2AOK Pege Akademie, AOK Nordost-Die Gesundheitkasse, Berlin, Deutschland

Zweck: Die Versorgung bei Pegebedürigkeit erfolgt in Deutschland

meistens durch Angehörige, nur teilweise unterstützt durch ambulante

Pegedienste und nur rund 25% in stationären Einrichtungen. Sie haben

somit in der pegerischen und sorgenden Begleitung in der häuslichen

Umgebung eine besondere Rolle. Zur Unterstützung dieser Situation ha-

ben Pegekassen nach §45 SGB XI den Aurag Pegekurse anzubieten,

in denen man praktische Pege und weitere Pegekompetenzen lernen

kann. Für Pegekassen ist von besonderem Interesse, ob für diese Kurse

zukünig besondere Aspekte der Pege von Menschen mit einer Krebser-

krankung zu berücksichtigen sind. Da schon lange nicht mehr jede Kreb-

serkrankung tödlich verläu, aber trotz guter Heilungschancen Spuren

hinterlässt, ist sie nicht mehr nur für die Akutpege, sondern auch für die

Langzeitpege von zunehmender Bedeutung. Neue Angebote zu onkolo-

gischen emen und zur Begleitung von Sterben und Tod sollen ggf. im

Spektrum der Pegekurse ergänzt werden.

Methoden: Pegebedürigkeit wird über einen Leistungsanspruch zur

Unterstützung in der Pegesituation über die Pegekassen erfasst. Die

Voraussetzung ist nach Antragstellung die Zuordnung eines Pegegrades.

Die Daten der AOK Nordost zur Pegebedürigkeit der Pegekasse

wurde in Verbindung mit Krebsdiagnosen aus der Krankenkasse be-

trachtet. Ergänzt wurden diese durch den jeweiligen Versorgungsort zum

Lebensende.

Ergebnisse: Bei der AOK Nordost gab es 2018 n=47.399 Pegebedürige

mit einer Krebsdiagnose. Von diesen werden 23% stationär, 42% zu Hause

ohne und 36% zu Hause mit Pegedienst versorgt. Ein Drittel davon sind

im Laufe des Jahres 2018 verstorben. Davon sind 2/3 der zu Hause Gep-

egten auch zu Hause gestorben.

Fazit: Es wird daher ein Bedarf gesehen, die Pege von Menschen mit

Krebserkrankungen und zur Begleitung am Lebensende, als emen für

zukünige Pegekurse für Angehörige zu implementieren.

Quellenangaben:

1. Daten zu Versicherten der AOK Nordost - Die Gesundheitskasse 2018

Oenlegungserklärung: kein Interessenskonikt

340

Pegerisches Beratungsprogramm in der ambulanten

Nachsorge stammzelltransplantierter Patienten

Norbert Hebestreit

Universitätsklinikum Jena, Pegedirektion, Jena, Deutschland

Purpose: Um angemessen auf das Problemprol stammzelltransplantierter

Patienten reagieren zu können, wurde ein pegerisches Beratungspro-

gramm entwickelt (6 Module): (1) Körperpege, (2) Aktivität/Ruhe, (3)

Ernährung/Sicherheit, (4) erapiekooperation, (5) Soziale Interaktion

und (6) Integrität der Person. Ziel der Studie ist es, die Wirksamkeit des

Programms zu überprüfen.

Methods: Das Programm soll sich fördernd auf die (a) Selbstpegekom-

petenz der Patienten auswirken, deren (b) Pegeabhängigkeit senken und

die (c) individuelle Lebensqualität steigern. Die Intervention wird über

eine RCT evaluiert. Die Interventionspatienten (IG) nehmen am komple-

mentären Beratungsprogramm teil. Die Kontrollpatienten (KG) werden

kliniküblich versorgt. Für alle drei Studienendpunkte (a, b, c) werden zur

Entlassung (T1), nach 3 Monaten (T2) und nach 6 Monaten (T3) Mess-

werte (ASA-A, PAS, SEIQoL-DW) erfasst.

Results: 62 Patienten wurden in die Studie aufgenommen. Die Ergebnisse

belegen von T1 nach T3 einen größeren Anstieg der Selbstpegekompe-

tenz (ASA-Punkte: IG 8,9 vs. KG 0,1; P < 0,01) und einen stärkeren Abfall

der Pegeabhängigkeit (PAS-Punkte: IG 8,5 vs. KG 4,4; P < 0,01) unter In-

tervention. Eekte bezüglich der Lebensqualität waren nicht nachweisbar.

Conclusions: Die Studienergebnisse bestätigen die positiven Auswirkun-

gen der Pegeberatung auf das Patientenoutcome. Damit werden Unter-

suchungsergebnisse unterstützt, welche den Nutzen vergleichbarer Inter-

ventionen in der Intermediär- und Spätphase nach HSCT belegen. Zur

Ergebnisbekräigung gilt es, Replikationen in größeren Stichproben zu

planen.

Disclosure Statement:

1. Anstellungsverhältnis oder Führungsposition

Keine

2. Beratungstätigkeit

Keine

3. Aktienbesitz

Keine

4. Honorare

Keine

5. Finanzierung wissenschalicher Untersuchungen

Keine

6. Gutachtertätigkeiten

Keine

7. Andere nanzielle Beziehungen

Keine

605

Pegerische Interventionen bei einem Hand-Fuß-Syndrom

bedingt durch eine Target- oder Chemotherapie: Eine

systematische Literaturübersicht

Nino Chikhradze 1; Sara Marquard 2; Melanie Pieper 3; Tabea Büter 3;

Dauer Bettina 4; Birgit Kröger 5; Gabriele Knötgen 6; Patrik Ristau 7;

Kerstin Schröder 8; Stefanie Seeling 9

1Ruhr-Universität Bochum, Bochum, Deutschland

2Universität Osnabrück, Osnabrück, Deutschland

3Krankenhaus Ludmillenstift, Meppen, Deutschland

4Philosophisch-Theologische Hochschule Vallendar, Vallendar, Deutschland

5Katholisches Krankenhaus Hagen gem. GmbH, Hagen, Deutschland

6Ubbo-Emmius-Klinik, Aurich, Deutschland

7Johanniter-Unfall-Hilfe e.V. Regionalverband Darmstadt-Dieburg

8Klinikum Bremen-Mitte, Bremen, Deutschland

9Hochschule Osnabrück – Campus Lingen, Lingen (Ems), Deutschland

Zweck: Menschen, die aufgrund einer onkologischen Erkrankung eine

Chemotherapie erhalten, leiden o unter einem Hand-Fuß-Syndrom

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Oncol Res Treat 2020;43(suppl 1):1–265 Abstracts144

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Index

2018

(HFS). In diesem Zusammenhang steigt die Bedeutung an unterstüt-

zenden Maßnahmen, die der Reduktion und Prophylaxe der Symptome

dienen. Diese internationale Literaturübersicht stellt die identizierten,

evidenzbasierten Pegeinterventionen bei einem HFS dar.

Methoden: Eine systematische Literaturrecherche erfolgte in Literatur-

datenbanken aus unterschiedlichen Disziplinen für den Zeitraum 01.2010

– 09.2019. Eingeschlossen wurden deutsch- oder englischsprachige wis-

senschaliche Publikationen. Die Qualitätsbewertung sowie Analyse

und Synthese der Studien, erfolgte von den Mitgliedern der Sektion der

Deutschen Gesellscha für Pegewissenscha e. V.

Ergebnisse: Für die Qualitätsbewertung konnten n=38 Publikationen in

die systematische Literaturübersicht eingeschlossen werden. Die Haupt-

themen der Literaturanalyse waren zum einen, allgemeine Vorgehens-

weisen pegerischer Intervention in der Prävention und Behandlung und

zum anderen spezische Planung von präventiven Maßnahmen je nach

erapieregime bzw. Medikamentengabe.

Fazit: Die Prävention und die Behandlung von HFS in der onkologischen

erapie ist in der Literatur sichtbar. Die Umsetzung dieser Interven-

tionen in der direkten Interaktion und durch edukative Konzepte sind

elementar für die bildende und begleitende Rolle der Pegefachkra.

Grundlage hierfür bilden therapienagepasste Interventionen sowie gute

kommunikative und agogische Kompetenzen der Pegenden.

Quellenangaben:

1. Bartal A, Mátrai Z, Szûcs A, Liszkay G.(2011). Main treatment and preventive

measures for handfoot syndrome, a dermatologic side eect of cancer therapy.

Magy Onkol.:91-8.

2. Fabbrocini G, Cristaudo A, Ionescu MA, Panariello L, Robert G, Pellicano M,

Ayala F. (2018). Topical non-occlusive polymers in hand-foot syndrome. G Ital

Dermatol Venereol;153(2):165-171.

Oenlegungserklärung: Es sind keine relevanten nanziellen Verbindungen

oenzulegen.

616

Versorgung von Patienten mit kolo-rektalem Karzinom:

Der Einsatz einer „Advanced Nursing Practice“ (ANP) Als

ergänzende Praxisoption

Roland Jusu Allieu

Münster, Deutschland

Purpose: Jährlich steigt die Zahl der diagnostizierten und behandelten

Patienten mit kolo-rektalem Karzinom. Um den Bedürfnissen dieser

Patienten gerecht zu werden, werden sie durch ein spezialisiertes inter-

disziplinäres Team versorgt, das auf eine systematische Beratung, Diag-

nostik, Behandlung und Nachsorge abzielt. Um die Behandlung dieser

Patienten auf pegerischer Seite zu optimieren, könnte eine „Advance

Nursing Practice“ (ANP) eingeführt werden. Dies erfordert jedoch eine

strategische Entwicklung, Implementierung und Evaluation dieses Ver-

sorgungskonzeptes und -modells. Das PEPPA-Framework bietet ein

Modell dafür. Gut funktionierende Konzepte oder Modelle sollen in die

Praxis umsetzen und durch weitere Forschung optimiert werden.

Das Ziel ist die Identizierung und Zusammenfassung von Tätigkeits-

feldern einer ANP im Rahmen der Versorgung von Patienten mit ko-

lo-rektalem Karzinom.

Methods: Zu diesem Zweck wurde eine systematische Literaturrecherche

in CINAHL durchgeführt. Diese ergab 22 Studien. Anhand der Abstrakte

konnten vier geeignete Studien identiziert werden, in welchen die Be-

deutung der ANP in der Patientenversorgung deutlich wurde, dennoch

fokussierten sich nur zwei auf das kolo-rektale Karzinom.

Results: Die Komplexität der Patientenversorgung und der Krank-

heitsverlauf und die Bedeutung eines multidisziplinären Teams setzt die

Entwicklung neuer Versorgungsmodelle voraus, wie zum Beispiel die Ein-

führung der ANP.

Conclusions: Eicher et. al. 2006 weisen darauf hin, dass ANP Interven-

tionen einen positiven Einuss auf die Patientenversorgung haben kann.

Dennoch mangelt es an primären Evidenzen hinsichtlich der Versorgung

von Patienten mit kolo-rektalem Karzinom.

765

Sensibilisierung von Pegenden auf tägliche Phänomene.

Eine Prozessoptimierung am Beispiel orale Mucositis

Timo Gottlieb

Universitätsmedizin Essen, Uniklinikum Essen, Essen, Deutschland

Zweck: Der Zweck dieser Arbeit ist die Sensibilisierung der Pegefach-

personen auf ihre Kernkompetenzen und die Abbildung dieser Ergeb-

nisse in Rahmen von sichtbaren Instrumenten. Hierbei soll der Pege die

Möglichkeit gegeben werden, Erfolge zu zeigen und diese präsentieren zu

können.

Methoden: Methodisch wurde in mehreren Schritten vorgegangen. Zu-

nächst wurde eine Literaturanalyse zum ema Orale Mucositis durch-

geführt und die neusten Erkenntnisse zusammengetragen. Im nächsten

Schritt wurde das Assessmentinstrument „Oral Mucositis Dayli Ques-

tionare“ durch die Pege ausgewählt und entsprechend in die Praxis im-

plementiert. In einer ersten Pilotphase von Vier Wochen wurde dies ge-

testet und dann evaluiert und anschließend ausgeweitet. Im letzten Schritt

wurden Fortbildungen in Form von „One Minute Wonder“ erstellt sowie

getestet und evaluiert.

Ergebnisse: Für die Pege hat sich schnell eine Zufriedene Haltung en-

twickelt, ihre Qualikationen abbilden zu können. Ebenso wurde im

interdisziplinären Kontext eine hohe Akzeptanz erreicht und das As-

sessment für die tägliche Visite zur Evaluation genutzt. Das Assessment

konnte mit wenigen Veränderungen eingeführt werden und hatte eine

leichte Anwendungsmöglichkeit.

Fazit: Als Fazit lässt sich deutlich aufzeigen, dass die Pege sich durch

Visualisierung der eigenen Ergebnisse motivieren lässt, sich diesem

Phänomen zu widmen und entsprechend an der Weiterentwicklung

mitzuarbeiten. Durch die Mitbestimmung an der Auswahl von Assess-

ment und emen für die OMW wird eine hohe Akzeptanz erwartet. Das

ema hat auch interdisziplinär einen anderen Stellenwert erreicht, wofür

die Pege Vorreiter ist.

Quellenangaben:

1. Leitlinienprogramm Onkologie (Deutsche Krebsgesellscha, Deutsche

Krebshilfe, AWMF): Supportive erapie bei onkologischen PatientInnen -

Langversion 1.1, 2017,

AWMF Registernummer: 032/054OL, http://leitlinienprogramm- onkologie.

de/Supportive-erapie.95.0.html (Zugri am 07.09.2019)

Oenlegungserklärung: Der Autor erklärt hiermit, keinen Interessenskonikt zu

haben

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Oncol Res Treat 2020;43(suppl 1):1–265Abstracts 145

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Index

2018

786

Basale Stimulation in der Onkologie. Wer protiert davon?

Anja Köhler

Universitätsklinikum Jena, KIM II, Abt. Palliativmedizin, Jena, Deutschland

Viele der Patienten mit denen wir täglich arbeiten, sind hoch betagt

oder leiden unter dementiellen Veränderungen. Sie haben cerebrale Me-

tastasen oder Tumoren des ZNS, sind durch einen Aufenthalt auf einer

Intensivstation beeinträchtigt, haben ein Delir, eine schwere Infektion,

Elektrolytverschiebungen oder benden sich am Lebensende. Es gibt aber

auch Patienten, welche aufgrund ihrer Fatigue oder ihrer ausgeprägten

körperlichen Schwäche tagsüber wie auch nachts schlafen. Alle haben sie

o eins gemeinsam: Sie verlieren die Orientierung. Der Alltag hat ein-

en ungewohnten Rhythmus, viele fremde Menschen sind um sie herum,

unbekannte Prozeduren müssen durchgeführt werden, der Lebensmittel-

punkt ist das Krankenbett. Der Patient und seine Angehörigen benötigen

in dieser krisenhaen Lebenssituation Unterstützung durch Pegende. In

diesem Vortrag möchte ich das Konzept der Basalen Stimulation® vorstel-

len und anhand von Beispielen, Möglichkeiten für eine kompetente und

empathische Pege und Begleitung dieser Menschen aufzuzeigen.

Psychooncology

Poster

Study on the Relationship between Patients with Advanced

Prostate Cancer and their Partners

Andreas Ihrig 1; Tobias Hanslmeier 1; Hans-Christoph Friederich 1;

Carsten Grüllich 2; Imad Maatouk 1

1Sektion Psychoonkologie, Universitätsklinik Heidelberg, Heidelberg,

Deutschland

2NCT, Universitätsklinik Heidelberg, Heidelberg

Purpose: e aim of the study is to identify possible dierences between

patients in an advanced stage of prostate cancer and their partners in the

areas of therapy decision, treatment goals, perception of cognitive chang-

es, stress and partnership. e results should contribute to a better under-

standing of this special life situation.

Methods: e study is a non-interventional explorative study. We inves-

tigated in 100 patients with advanced prostate cancer and their partners

who completed their own questionnaires. Anamnestic, psychological (dis-

tress thermometer, PHQ-4, EORTC:global quality of life, ASKU, PA-F)

and partnership (QMI-D) questionnaires are used.

Results: e partners are younger than the patients (64.6 vs. 69.2 years).

No signicant dierences were found in quality of life, subjective com-

petence expectation and depressiveness. However, the partners reported

higher distress (5.7 vs. 4.8), anxiety (1.9 vs. 1.4) and fear of progression

(33.9 vs. 30.8). Trends toward worsening are reported in all 13 questions

on core symptoms of dementia. e most pronounced deteriorations are

in the area of emotional balance, motivation to do something, to perform

movements correctly and to organize everyday things. Partners rate the

limitations in 9 of the 13 questions more highly than the patients them-

selves. With regard to the therapy decision, a decision based on partner-

ship is usually preferred, with the emphasis on the patient’s will. Only 6%

of the patients state that they make the therapy decision without involving

their partner. e quality of the partnership is rated better by the patients

(42.4 vs. 40.6) than by the partners.

Conclusions: Apart from the fact that both groups are psychologically

highly stressed, the partners show a pronounced anxiety symptomatology

while the patients suer from a deterioration of cognitive abilities. Due

to the high stress of these couples and the involvement of the partners in

the therapy decision, it is important that the attending physician provides

detailed information and support to both.

Disclosure Statement: None

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Identifying Subtypes of the Psycho-Neurological Symptom

Cluster in Long-Term Prostate Cancer Survivors – Results from

the Multiregional Procas Study

Salome Adam 1; Melissa S.Y. Thong 2; Eva Martin-Diener 3; Bertrand

Camey 4; Celine Egger Hayoz 4; Isabelle Konzelmann 5; Seyed Mohsen

Mousavi 6, 7; Christian Herrmann 6, 7; Sabine Rohrmann 8; Miriam Wanner 8;

Katharina Staehlin 9; Räto Strebel 10; Marco Randazzo 1; Hubert John 11;

Hans-Peter Schmid 12; Anita Feller 1; Volker Arndt 1, 2

1National Institute for Cancer Epidemiology and Registration (NICER), Zurich,

Schweiz

2Unit of Cancer Survivorship, German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

3Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and

Prevention Institute, University of Zurich, Zurich, Schweiz

4Fribourg Cancer Registry, Fribourg, Schweiz

5Health Observatory Valais, Valais Cancer Registry, Sion, Schweiz

6Cancer Registry East Switzerland, St. Gallen, Schweiz

7Cancer Registry Graubünden and Glarus, Chur, Schweiz

8Cancer Registry Zurich and Zug, Zurich, Schweiz

9Basel Cancer Registry, Basel, Schweiz

10Department of Urology, Graubünden Cantonal Hospital, Chur, Schweiz

11Department of Urology, Winterthur Cantonal Hospital, Winterthur, Schweiz

12Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Schweiz

Purpose: Aside from common urological and sexual problems, long-term

(≥5 years aer diagnosis) prostate cancer (PC) survivors might suer from

pain, fatigue and depression. ese symptoms are collectively known as

the psycho-neurological symptom (PNS) cluster. No research has been

done to 1) identify possible subtypes of this cluster, 2) classify cancer sur-

vivors accordingly, and 3) explore associations between subtypes of the

PNS cluster and health-related quality of life (HRQoL) in long-term PC

survivors.

Methods: e study sample included 653 stage T1-T3N0M0 long-term

PC survivors, identied from the multiregional Prostate Cancer Survi-

vorship in Switzerland study. Briey, in 2017/2018, PC survivors were

identied via six population-based cancer registries based in both Ger-

man- and French-speaking Switzerland. Fatigue was assessed with the

EORTC QLQ-FA12, mental health with the MHI-5, and pain with the

EORTC QLQ-C30 questionnaire. Latent class analysis was used to derive

PNS cluster classes. Factors associated with the derived classes were deter-

mined with multinomial logistic regression analysis.

Results: ree PNS classes were identied: class 1 (n=394, 61.4%) – ‘low

pain, physical and emotional fatigue, moderate mental distress’; class 2

(n=98, 15.1%) – ‘low physical fatigue and pain, moderate emotional fa-

tigue, high mental distress’; and class 3 (n=151, 23.5%) high scores for all

symptoms. Survivors in class 2 and 3 were more likely to be less physical-

ly active, having a comorbidity, being treated with radiation therapy, and

having worse HRQoL outcomes compared to class 1 (reference).

Conclusions: ree distinct classes of the PNS cluster were identied,

which could be distinguished by treatment, comorbidities, lifestyle factors

and HRQoL outcomes. erefore, improving classication of PC survi-

vors according to severity of multiple symptoms could assist in developing

interventions tailored to survivors’ needs.

Disclosure Statement: e authors have nothing to disclose.

Expectations and Experiences with the term

“Immunotherapy” in the Context of Cancer

Jennier Richter; Andreas Ihrig; Imad Maatouk

Heidelberg, Division of Psychooncology, Department of General Internal

Medicine and Psychosomatic, University Hospital Heidelberg, Heidelberg,

Deutschland

Purpose: e aim of our study was to describe expectations and expe-

riences of patients, physicians and employees of the cancer information

service with immune checkpoint inhibitors (ICIs) in cancer therapy.

Methods: In this mixed methods study we investigated knowledge, ideas

and believes of 108 cancer patients and 53 patients without cancer about

ICIs. For this purpose we used a structured questionnaire. We also inter-

viewed 12 patients which were currently receiving ICI therapy. In order to

examine the health professionals´ perspective we performed focus groups

with 8 physicians and 9 employees of the cancer information service.

Results: In the patient groups we could identify a lack of knowledge re-

garding the ICIs. 38% of the patients with ICI therapy were not able to

describe the mechanism of the therapy without relevant false contents. In

patients without ICI therapy this percentage was even 87%. Furthermore,

the results suggest that the image of immunotherapy is noticeably better

than that of CT. Immunotherapy is considered to be more expensive, but

also in lesser time, more promising and with a lower spectrum of side

eects. In patients´ opinion, the future rather belongs to immunothera-

py than to CT. In the qualitative interviews, the patients focused on the

topics “prognosis”, “quality of life”, “therapy decision” and “side eects”.

e participants of the focus groups discussed more about topics such as

“creation of an information base” and “how immunotherapy is portrayed

in the media”.

Conclusions: Personal conversation between patients and physicians

should have the highest priority to create an information base for the pa-

tient. Furthermore, evidence-based tools, which provide information on

ICIs to patients, would be desirable. Based on the good rating of the ICI

therapy, it might be useful during therapy education to ensure that possi-

ble side eects are not underestimated by the patients.

Disclosure Statement: ere are no nancial conicts of interest to disclose.

Loh-Fear: Determination of Subjectively Perceived Anxiety of

Patients inOncological Abdominal Surgery

Benedikt Kunzmann 1; Jan Brederecke 2; Lea Harms 3; Thomas Jungbluth 1;

Tanja Zimmermann 2; Jens Harms 1

1Klinik für Allgemein- und Viszeralchirurgie, Klinikum Wolfsburg, Wolfsburg,

Deutschland

2Klinik für Psychosomatik und Psychotherapie, Mediznische Hochschule

Hannover, Hannover, Deutschland

3Columbia University New York, Department of Obestetrics and Gynecology,

New York, United States

Purpose: For many patients visceral oncological surgery is associated with

anxiety, such as fear of heteronomy, pain, injury, physical disgurement,

complications and death. e present study measures anxiety in patients

both in intensity and over time.

Methods: In N= 100 persons with a malignant gastrointestinal tumor (62

men, 38 women; age: M = 68.4 years; SD=10.8; 36-89) anxiety, depression

and distress was assessed at 4 time points: rst contact (T1), inpatient ad-

mission (T2), hospital discharge (T3) and 30 days post inpatient discharge

(T4).

Results: Subjectively perceived anxiety and depression was highest at T1

and at T3. 30% of patients showed increased values above the cut-o, re-

garding anxiety and depression at T1. Higher values of fear at T1 did not

correlate in regards to levels of fear at T4 in comparison with patients ex-

hibiting low values of fear at T1. In the framework of a logistical regression

a high subjectively perceived burden at T1 was attached to elevated levels

of fears at T3 and T4. A multifactor analysis was performed.

Conclusions: Anxiety and depression appear to be an ongoing problem.

e identication of persons at risk for clinically relevant anxiety or de-

pression is a particular challenge. Since the extent of anxiety varies over

time, a one- o assessment of anxiety at the beginning is not sucient.

However, the subjectively perceived level of distress seems to be a valid

predictor for anxiety at the end of treatment. In the course of treatment,

the highest anxiety and depression values were found at initial contact and

inpatient discharge. Reasons for a lower expression during the treatment

phase may be due in the medical and nursing care and competence and

the subjective feeling of “being cared for”. e results verify the relevance

of screening tools for psychological burden also in oncological visceral

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surgery. Furthermore the question arises as to which psycho- oncological

interventions appear to be indicated and feasible in the pre- and periop-

erative setting.

Disclosure Statement: e authors declare that they have no conict of interest.

144

Benet-Finding in Long-Term Prostate Cancer Survivors

Irène Lassmann 1; Andreas Dinkel 2; Birgitt Marten-Mittag 2;

Helga Schulwitz 1; Jürgen E. Gschwend 1; Kathleen Herkommer 1

1Klinik und Poliklinik für Urologie, Technische Universität München, Fakultät für

Medizin, Klinikum rechts der Isar, München, Deutschland

2Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Technische Universität München, Fakultät für Medizin, Klinikum rechts der Isar,

München, Deutschland

Purpose: Benet-nding (BF) refers to positive eects that may arise in

the aermath of a cancer diagnosis. It involves disease-induced changes in

dierent aspects of personal and social life such as enhanced interpersonal

relationships or growing acceptance of life’s deciencies. e aim of the

current study was to investigate the extent of BF and its determinants in

prostate cancer (PC) survivors.

Methods: 4,252 PC survivors (97.9% radical prostatectomy) from the

German database “Familial PC” were available for analysis. Association

between BF (German version of the Benet-nding-scale) and sociode-

mographic and clinical variables was analyzed using bivariate analysis.

Results: Mean age at survey was 77.4±6.2 years with a mean follow-up of

14.8±3.8 years. 29.4% of the respondents owned a university degree, 85.4%

were living with a partner and 25.1% perceived the severity of the disease

as high. 19.6% had a biochemical recurrence at time of survey and 13.5%

were under PC-treatment. Mean BF-score was 3.1±1.0 (range 1-5), 59.7%

had a BF-score ≥3, 22.6% had score of ≥4. Highest BF-scores emerged for

the items “taught me to adjust to things I can`t change” (3.6±1.2), “has

helped me take things as they come» (3.6±1.2), and “has shown me that

all people need to be loved” (3.5±1.4). Higher BF-level was associated

with lower educational level and with higher perceived severity of the PC

(p<0.001). Time since diagnosis, biochemical recurrence, ongoing treat-

ment as well as anxiety and depression (patient health questionnaire-4)

showed statistically signicant but negligible associations with BF.

Conclusions: 60% of long-term PC survivors expressed moderate-to-high

levels of BF. Higher perceived severity of the disease as well as a lower ed-

ucational level were associated with higher levels of BF. In contrast, the

clinical course of the PC (past or present biochemical recurrence, ongoing

treatment) had no clinically meaningful eect on the amount of found

benet.

Disclosure Statement: No conict of interest.

151

Physical Exercize, Coping, and Survival in Cancer Patients

Volker Tschuschke 1; Elke Jäger 2; Margarete Ruppert 3

1Köln, Universitätsklinik, Köln, Deutschland

2Frankfurt am Main, Klinikum Nordwest, Frankfurt am Main, Deutschland

3Daimlerstraße 12, Palliativteam Hochtaunus, Bad Homburg, Deutschland

Purpose: A growing number of studies supports the positive connection

between physical exercise training programs and improved quality of life

in cancer patients. Some studies even suggest that an increased physical

activity may contribute to a better survival of such patients. We report

results of an exercise intervention program in patients by also controlling

for psychological and coping ressources with regard to survival time.

Methods: 82 patients with advanced cancer diseases of various kinds

received an individually tailor-made exercise training over six weeks.

Gain in lung capacity (VO2max) was controlled by comparing pre and

post VO2max. Patients completed the EORTC QLQ-C30 questionnaire,

Prole of Mood Scales (POMS), SCL-K and were interviewed with a semi-

structured interview with regard to their coping ressources at baseline

and aer the exercise intervention. Independent blind raters objectively

rated the interviews sentence by sentence using the Ulm Coping Manual

(UCM). Survival time was followed for more than eight years.

Results: Linear mixed-model analyses revealed that specic active cop-

ing ressources and sucient role functions predicted gain in VO2max and

VO2max in turn predicted survival time besides signicant increases in

two active coping dimensions: information seeking and anticipation.

Conclusions: Psychological and personality variables such as coping res-

sources are essential predictors for cancer patients’ benet from exercise

training.

208

Integration of Cross-Sectoral Psycho-Oncological Care into

Inpatient and Outpatient Cancer Therapy

Steen Krebs 1; Jennifer Benner 2; Lukas Matyschik 3; Karin Osborne 4;

Jürgen Wolf 1; Michael Kusch 1

1Centrum für Integrierte Onkologie - CIO Köln, Universitätsklinikum Köln, Köln

2GFO Kliniken Troisdorf, Standort St. Josef, Troisdorf

3Johanna-Etienne-Krankenhaus, Neuss

4Kliniken Mariahilf, Mönchengladbach

Purpose: e National Cancer Plan describes the objective of cross-sec-

tor, integrated oncological care (eld of action 2, objective 7). Coopera-

tion and coordination in oncological care across sectors and occupational

groups should be improved and self-help more closely integrated. e

isPO project (integrated, cross-sectoral psycho-oncology), funded by the

Innovation Committee of the Federal Joint Committee, aims to integrate

psycho-oncology into inpatient and outpatient care through vertical and

horizontal coordination and cooperation.

Methods: In the isPO project, a psycho-oncological care programme will

be developed, implemented and evaluated by 2021. e integration of the

programme into oncology will be implemented through the establishment

of psycho-oncological care networks consisting of an oncological centre

and registered doctors (vertical cooperation) as well as the (horizontal)

cooperation of doctors, nurses/medical assistants, psychotherapists, psy-

chosocial specialists and self-help. A network coordinator takes over the

central control of the processes and is the contact person for all profes-

sional groups.

Results: e program will be integrated at four locations (Cologne, Trois-

dorf, Neuss, Mönchengladbach) as part of a contract pursuant to § 140a

SGB V. It is presented in the form of organization charts with dened tasks

and powers and is implemented on the basis of formal administrative

SOP´s . e programme has been undergoing testing since the beginning

of 2019. It is evaluated and optimized within the framework of a qual-

ity management system. e main outcome criteria for integration are

(timely) patient enrolment and cross-sector networking of care.

Conclusions: e establishment of cooperation and coordination struc-

tures integrated into the oncological care routine is essential if all cancer

patients are to be oered psycho-oncological care, as required by the Na-

tional Cancer Plan.

References: not applicable

Disclosure Statement: e authors declare that they have no conict of interests.

231

Factors Inuencing Psychosocial Distress in Persons with

Hereditary Cancer Predisposition Syndromes and their

Relatives - “Gemeinsamgen”

Josene Fischer-Jacobs 1; Anna Maria Kastner 1; Andrea Hahne 2;

Tanja Zimmermann 1

1Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical

School, Hannover, Deutschland

2BRCA Netzwerk e.V., Bonn, Deutschland

Purpose: Persons with hereditary cancer predisposition syndromes car-

ry a mutation in individual genes and hence are at increased risk for the

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development of specic tumors (e.g., HBOC, HNPCC, Gorlin Syndrome).

Typically the age of onset is earlier and a familial accumulation of the syn-

drome-specic tumor spectrum is seen. e knowledge of a genetic dispo-

sition can relieve aected families, providing the possibilities of prophy-

lactic surgeries and intensied surveillance for early detection. As well as

precipitate psychological stress. Specic factors that can lead to increased

distress involve, e.g., coping behavior, psychosocial problems, familial is-

sues, feelings of guilt and fear of developing cancer. Whether and to what

extent relatives experience distress has not yet been suciently investi-

gated. is study therefore aims to gain knowledge about stress inducing

factors in mutation carriers and relatives.

Methods: Within the scope of a nationwide, cross-sectional online sur-

vey mutation carriers and relatives will be asked about their subjectively

experienced psychological distress via patient reported outcomes N=236

individuals will be included. In addition, questionnaires are used to record

individual and family factors for which a correlation is assumed.

Results: For the statistical analysis we assume a nal N of 118 per group

(N=236). Besides descriptive evaluations, such as mean values, standard

deviations and frequencies, regression analyses are planned. First results

will be presented at the conference.

Conclusions: e research ndings can help towards identifying predic-

tors of psychosocial distress as well as determining specic risk groups.

Consequently, feasible decits in the quality of care can be detected. Fur-

thermore the results can be implemented in the development of further

psychosocial care services and interventions. In particular this study can

make an important contribution to assessing the psychosocial burden of

relatives, given that only little research on these individuals has been con-

ducted so far.

237

“And Now, Am I Ill or Still Healthy?” Psychological and

Medical Need for Assistance in Women with Increased Risk

for Hereditary Breast- and Ovarian Cancer – A Qualitative

Analysis

Josene Fischer-Jacobs 1; Schlegelberger Brigitte 1; Martina de Zwaan 1;

Tanja Zimmermann 2

1Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical

School, Hannover, Deutschland

2Department of Human Genetics, Hannover Medical School, Hannover,

Deutschland

Purpose: Healthy women recognized to carry a pathogenic BRCA1/2 mu-

tation bear a signicant psychological burden, e.g. due to uncertainty how

to deal with an increased risk to develop breast (BC) and ovarian cancer

(OC). Mutation carriers may experience signicant levels of distress in the

short time, and genetic testing distress can remain elevated in the longer

term, especially among younger women and women with higher levels of

distress at testing. Only one-third of the counselees who reported a re-

quest for psychological assistance had attained help. is study aims to

identify whether, and if so, in which extent women with hereditary BC

and OC need psychological and medical assistance and which contents

could be additionally of interest for them.

Methods: N = 21 women were asked by in-depth interviews if a genetic

burden exists and if psychological assistance were requested. In addition,

topics of interest were identied. Moreover, N = 5 interviews were con-

ducted with experts (physicians, psycho-oncologists) to identify themes

of interest for women with a pathogenic mutation.

Results: Preliminary analysis indicates that 33.3% requested for psycho-

logical help because of the genetic mutation and/or their consequence in

the past (divorce, depression). Further, 52.4% of the interviewed women

show an interest in psychological help. At this point main topics are com-

munication within relatives, anxiety, decision-making processes, dealing

with genetic- and family-related distress. Relatives and their way to cope

with the mutation are of particular importance for aected people. More

extensive analyses are planned.

Conclusions: In particular this study takes rst step toward understanding

patients’ psychological and medical need for assistance and suggested

main themes of interest. A long-term goal could be the development of

further psychosocial care services and interventions. In Addition further

research is needed which focus on relatives, because whether and to

what extent relatives experience distress has not yet been suciently

investigated.

243

Spiritual Care in Oncology: Cancer Patients’ Unmet Spiritual –

Data from a Pilot Project

Arndt Büssing 1; Jens Büntzel 2; Eckhard Frick 3

1Professorship Quality of Life, Spirituality and Coping, Institute of Integrative

Medicine , Witten/Herdecke University, Herdecke, Deutschland

2Department of Otolaryngology, Palliative Care Unit, Südharz Clinic

Nordhausen, Nordhausen, Deutschland

3Research Unit Spiritual Care, Clinic for Psychosomatic Medicine and

Psychotherapy, Technical University Munich, München, Deutschland

Purpose: As part of the AG PRIO project on spiritual needs of cancer

patients, we analyzed their unmet spiritual needs and related these to their

interpretations of illness (IoI) and quality of life.

Methods: Cross sectional survey in a dened time frame among patients

with cancer (N=171; 62% women; 61±12 years of age; 53% R-S-) from

centers in East and West Germany with standardized questionnaires. Un-

met spiritual needs (SpNQ-20) were categorized as Religious (RN), Exis-

tential (ExN), Inner Peace (IPN), Generativity (GN) needs with intensity

scores ranging from 0 to 3.

Results: RN (0,8±0,9) and ExN (0,8±0,8) scored low, IPN (1,6±0,9) and

GN (1,4±0,9) higher. ere were no signicant dierences between East

and West. eir needs were moderately (r 0.3-0.5) related to positive IoI,

while negative IoI were related moderately to ExN and IPN only. IPN were

weakly (r 0.2-0.3) related to lower wellbeing (WHO5) and life satisfaction

(BMLSS-10), and positively with under pressure feelings (VAS); RN and

GN were not signicantly related. Patients with higher tumor stages had

signicantly higher ExN, IPN and GN, but not RN.

Conclusions: Identifying cancer patients´ unmeet spiritual needs requires

a reaction from health professionals and pastoral workers. ese needs

were related to higher tumor stages, how they perceive their illness and

lower wellbeing - but not RN. us, health professionals do not have to

fear responding to strictly religious issues they may feel less competent

to address.

Disclosure Statement: e study was supported by a grant of German Cancer

Society. e authors disclose any conict of interest.

246

Dimensionen Der Patientenkompetenz Bei Krebsbetroenen:

Ergebnisse Einer Replikationsstudie im Vergleich

Juergen M. Giesler 1; Christine Holmberg 2; Joachim Weis 3

1Sektion Versorgungsforschung und Rehabilitationsforschung,

Universitätsklinikum Freiburg, Freiburg, Deutschland

2Institut für Sozialmedizin und Epidemiologie, Medizinische Hochschule

Brandenburg Theodor Fontane, Brandenburg an der Havel, Deutschland

3Stiftungsprofessur Selbsthilfeforschung, Tumorzentrum/CCC Freiburg,

Universitätsklinikum Freiburg, Freiburg, Deutschland

Purpose: Advancing Patient Competence (PC) represents an important

goal of Germany’s National Cancer Plan. However, no consensus has yet

been reached as to which dimensions may constitute PC. erefore, this

study asked whether the 8 dimensions of PC derived by Giesler and Weis1

would replicate in other samples of cancer patients.

Methods: Based on a sample of N = 424 breast, colorectal, and prostate

cancer patients (mean age 62 years, 53% female) undergoing either on-

cological rehabilitation or treatment in specialized oncology practices,

conrmatory factor analyses were performed for the problem- and the

emotion-focused items of the Patient Competence Questionnaire 57.1

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Results: Using conventional t criteria, 7 factors were identied for prob-

lem-focused items (e.g. seeking information, self-regulation, and assert-

ively interacting with physicians; CFI = .921, RMSEA = .054). For emo-

tion-focused items 3 factors were identied (managing distress, dealing

with threat, and (low) avoidance; CFI = .961, RMSEA = .055).

Conclusions: is study partially conrms the dimensions of PC found

by earlier research.1 Studies of similar intent report comparable results, in-

cluding a splitting of factors.2,3 us, the factors listed in the results section

appear to be replicable dimensions of PC with some restrictions. Future

research should focus on renements of the concept of PC and on inter-

ventions to advance it.

References:

1 Giesler JM, Weis J. Developing a self-rating measure of patient compe-

tence in the context of oncology: a multi-center study. Psychooncology.

2008;17(11):1089-1099.

2 Ralf L. Konrmatorische Überprüfung der dimensionalen Struktur des FEPK-

57 bei Patienten mit Prostatakrebs und Patientinnen mit Brustkrebs. Freiburg/

Br.: Pädagogische Hochschule Freiburg;2015.

3 Giesler JM, Holmberg C, Müller-Nordhorn J, Weis J. Conrmatory Factor

Analyses of the Patient Competence Questionnaire 57 in a Sample of Colorec-

tal Cancer Patients. Freiburg/Br.: Medical Center, University of Freiburg; 2019.

Disclosure Statement: e authors have no conict of interest.

268

Correlation of Psychooncological Support and Quality of Life

in Patients with Oral Cancer: A Study Based on an Electronic

Psychooncological Screening Instrument and Quality of Life

Questionnaire

Sebastian Hoefert 1; Norbert Schäeler 2; Martin Wickert 2; Siegmar

Reinert 1

1Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,

Universitätsklinikum Tübingen, Tübingen

2Psychosomatische Medizin und Psychotherapie, Universitätsklinikum

Tübingen, Tübingen, Deutschland

Purpose: Cancer patients suer from severe distress, and oral cancer pa-

tients report some of the highest distress levels of all cancer patients1. e

German S3-Guidline and the certied Head and Neck Cancer Centres

recommend psychooncological support for these patients. is study ana-

lysed the need for psychooncological support with an electronic screening

instrument (ePOS) and measured the Quality of Life (QoL) up to one year

aer therapy.

Methods: e ePOS instrument included the DISTRESS questionnaire

(DT), the Hornheider Screening Instrument (HSI), Hospital Anxiety and

Depression Scale (HADS), and inquiries for personal support need. ese

patients were also monitored with the EORTC QLQ-C30 and H&N35

QoL questionnaires.

Results: A total of 66 patients were screened including 37 patients with

QoL surveys completed aer one year: 76% of patients reached the

pre-therapeutic QoL level. Patients who opted for psychooncologial sup-

port had a signicantly worse QoL aer one year compared to patients

who tested positive for treatment need but did not request psychoonco-

logical support. e HADS was a predictive marker for a lower QoL aer

1 year.

Conclusions: Generally, a positive ePOS test for psychooncological sup-

port was not a signicant predictor for lower QoL outcome aer one year.

Patients who requested support showed a lower outcome in QoL. Con-

sequently, these patients should be supported more intensively. Patients

with a positive HADS may also benet from more intensive psychoonco-

logical support2. Our study was one of the rst analysing the pre-thera-

peutic distress and QoL outcome aer surgical cancer treatment.

References:

1. Dunne S et al. Psychological variables associated with quality of life following

primary treatment for head and neck cancer: a systematic review of the litera-

ture from 2004 to 2015. Psychoncology 26:149-160 (2017)

2. Handschel J et al. Psychological aspects aect quality of life in patients with

oral squamous cell carcinomas. Psycho-Oncology 22: 677-682 (2013)

Disclosure Statement: Nothing to disclose

304

Prognostic Awareness Regarding the Treatment Intensity in

Cancer Patients

Filipa Krolo 1; Martina Preisler 2; Meike Watzlawik 1; Amy Rohrmoser 3;

Ute Goerling 3; Anne Letsch 2

1Sigmund Freud PrivatUniversität Berlin, Fakultät für Psychologie, Berlin,

Deutschland

2Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Medizinische

Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,

Berlin, Deutschland

3Charité – Universitätsmedizin Berlin, Charité Coprehensive Cancer Center,

Berlin, Deutschland

Purpose: Higher levels of patients´ prognostic awareness (PA), crucial

for early integration of palliative care in oncology, lead to better decision

making about further treatment and care options. However, previous

studies have found mostly low levels of PA in patients. Focussing on PA

regarding the treatment intensity (PATI) as one facet of PA, the patients´

perception of the treatment intensity and possible discrepancies between

them and their oncologists regarding PA were explored.

Methods: Five cancer patients of a large German university hospital

were interviewed about their perception of the treatment intensity. e

interviews were analysed with Kuckartz´s thematic content analysis. e

patients and their oncologists completed questionnaires assessing the pa-

tients’ PA, too.

Results: e questionnaires showed moderate to high levels of congru-

ence between patients’ and oncologists’ answers, indicating moderate to

high levels of PA in patients. e following factors were reportedly im-

pacting their perception of the treatment intensity: the physical condition,

hope for recovery and normality, conditions in the hospital, interaction

with oncologists, social and nancial factors and psychological condition.

Conclusion: Knowing the patients´ individual background and their per-

ception of the treatment intensity is a key factor for improving PATI. e

factors inuencing the perception of treatment intensity can be assessed

via tailored questions. If healthcare professionals address these topics,

they may meet specic communication needs of the patients, leading to

higher levels of PATI.

References:

1. Applebaum AJ, Kolva EA, Kulikowski JR, et al (2014) Conceptualizing prog-

nostic awareness in advanced cancer: A systematic review. J Health Psychol.

9:1103–1119.

2. Temel JS, Greer JA, Muzikansky A, et al (2010) Early palliative care for patients

with metastatic nonsmall-cell lung cancer. N Engl J Med 363:733–42.

3. Kuckartz, U (2007) Einführung in die computergestützte Analyse qualitativer

Daten. VS Verlag, Wiesbaden.

Disclosure Statement: No conicts of interest.

375

Development and Evaluation of an Unguided Psychosocial

Online-Intervention for Caregivers of Cancer Patients (OAse):

Results of a Feasibility Study

Miriam Grapp 1, 2; Johanna Ell 1; Hans-Christoph Friederich 2;

Imad Maatouk 1, 2

1Universitätsklinikum Heidelberg, Psychonkologische Ambulanz am Nationalen

Zentrum für Tumorerkrankungen, Heidelberg, Deutschland

2Universitätsklinikum Heidelberg, Klinik für Allgemeine Innere Medizin und

Psychosomatik, Heidelberg, Deutschland

Purpose: Informal caregivers (family and friends) of cancer patients pro-

vide support to the patient and at the same time they experience an in-

creased burden or distress - oen unprepared for their caregiving role.

Due to shame, uncertainty or lack of time, psychosocial face-to-face ser-

vices are rarely used by cancer caregivers. e aim of this study is therefore

to develop and evaluate an unguided psychosocial online-intervention for

caregivers of cancer patients (OAse).

Methods: From June 2018 to April 2019, n=41 caregivers of cancer pa-

tients (spouse, children, friends) were included in the study. Participation

in the study was independent of patients’ tumour site and treatment stage.

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OAse is a resource-oriented, web-based unguided self-help program com-

prising four modules (understanding and providing eective support, un-

derstanding the patient’s feelings, dealing with own burdensome feelings,

strengthening own resources). Qualitative and quantitative data were col-

lected at the beginning (T1) and at the end (T2) of the intervention to

assess the feasibility and acceptance of OAse as well as patient satisfaction

with the program.

Results: Of the 41 caregivers 65,9% (n=27) were female. Most of the par-

ticipants were spouses (70,7%, n=29), followed by adult children (19,5%,

n=8) and friends (9,8%, n=4). e age of participants ranged from 19 to

69 years (M=44,59, SD=13,75). Of the 41 participating caregivers, n=28

(62.2%) fully completed the OAse intervention. e qualitative and quan-

titative data show a high degree of caregivers’ satisfaction.

Conclusions: Up to now specialised psychological internet interventions

for caregivers of cancer patients are rare. In the present study OAse has

proven feasible and acceptable. Compared to other unguided online

interventions in this eld, the completion rate was very high. erefore,

the intervention could make a signicant contribution to improve

caregivers’ psychological condition and to increase their competency and

self-ecacy.

Disclosure Statement: Authors have no conicts of interests.

408

Is the Spectrum of Mental Disorders in Cancer (Ca) Patients

Changed by Time?

Michael Brinkers 1; Anne-Marie Toeper 2; Giselher Pfau 1; Frank Meyer 3

1Klinik für Anästhesiologie und Intensivtherapie Uni Magdeburg,

Schmerzambulanz, Magdeburg, Deutschland

2Klinik für Augenheilkunde, Uni Magdeburg, Magdeburg

3Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Uni

Magdeburg, Magdeburg

Purpose: In a previous study, the spectrum of mental disorders of long-

term cancer(Ca) survivors (LCS; time since initial diagnosis, 5 years[yr]

as minimum) and patients with acute Ca pain (acpp; initial diagnosis, 1-2

yr ago) was compared. ere were dierences in the total number of men-

tal disorders (LCS: 65.6%; acpp: 53.8%) as well as, among them, organic

mental disorders (9.8% vs. 2.2%) and addictions (13.1% vs. 2.2%). Ca of

the urogenital tract (uro-Ca) were more frequent in LCS and gastrointes-

tinal(GI) Ca in acpp. Since uro-Ca in general has usually a longer survival

time, the question arose whether the dierent prevalences are a function

of the duration.

Hypothesis: If the dierent numbers were a consequence of the type of

Ca, this distribution would also be apparent in acpp of the urogenital tract.

Methods: “acpp” of the GI and urogenital tract were compared. e occur-

rence and distribution of mental disorders (F1-F4 according to ICD-10,

as well as psychologically normal ones) were investigated.

Results: Within the same period of time since initial diagnosis (GI=1.10

yr, Uro=1.37 yr), 50% of the GI patients had abnormal psychological nd-

ings, however, only 38.2% of the uro-patients. Addictions were found in

only 2.3% of uro Ca patients (ucp). Organic mental disorders were found

in 11.6% of ucp.

Conclusions: e acute ucp had less psychological disorders than the

acute GI-patients and, in particular, than LCS. is also applies to ad-

dictions. Derived from this, it can be assumed that mental disorders as a

specic group of patients as well as the individual diagnosis of addiction

develop to higher proportions over time.

is is in contrast to organic mental disorders, which already occur

as oen in acute ucp as in LCS. Here, the inuence of Ca diagnosis must

be assumed.

Disclosure Statement: Patients with a long history of Ca need to be examined for

the spectrum of various mental disorders, especially for addiction.

428

How Do Cancer Patients Experience Molecular Diagnostics?

Theresia Pichler 1, 2; Amy Rohrmoser 3; Anne Letsch 3, 4;

Benedikt Westphalen 1, 5; Ulrich Keilholz 3; Volker Heinemann 1, 5;

Peter Herschbach 1, 6; Ute Goerling 3

1Comprehensive Cancer Center München, München, Deutschland

2Klinikum rechts der Isar der Technischen Universität München, München,

Deutschland

3Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,

Berlin, Deutschland

4Charité – Universitätsmedizin Berlin, Medizinische Klinik für Hämatologie und

Onkologie, Campus Benjamin Franklin, Berlin, Deutschland

5Klinikum der Universität München, Medizinische Klinik und Poliklinik III,

München, Deutschland

6Klinikum rechts der Isar der Technischen Universität München, Klinik und

Poliklinik für Psychosomatische Medizin und Psychotherapie, München,

Deutschland

Purpose: Research ndings within molecular diagnostic (MD) raise

hope for new eective cancer treatments. At the same time, evidence of

a treatment benet of MD is still limited for many malignancies. How-

ever, patients may hold high expectations nonetheless. To support these

patients suciently, deeper insight into their individual experience with

MD is needed. us, this study examines cancer patients’ perceived level

of information and expectations regarding MD.

Methods: In two German Comprehensive Cancer Centers, 30 cancer

patients undergoing MD participated in semi-structured interviews on

their subjective level of information and expectations regarding their MD

participation. Additionally, socio-demographic, medical, and distress data

was collected.

Results: While most patients understood their program’s procedures,

many found the background of tumor genomic proling to be too com-

plex. In the tension between limited understanding and uncertainty about

a personal benet, they emphasized the importance of trusting their

doctor. Overall, patients mentioned three expectations of participating

in MD: 1) improving their treatment, 2) contributing to research and 3)

learning more about their tumor. Moreover, they described feeling indi-

vidually appreciated and maintaining hope for recovery by participating

in the MD program.

Conclusions: e results underline the signicance of the relationship

between patients and their oncologist within MD: Trusting their treating

physician can buer incomprehensible or missing information as well as

the uncertainty whether they will benet from MD at all. Also, patients

felt they were treated in a more “personalized” way. To balance patient

hopes and potential outcomes, oncologists and psycho-oncologists should

regularly and openly discuss treatment expectations as well as realistic

goals with their patients, thereby providing support and enabling an indi-

vidual and truly “personalized” treatment.

Disclosure Statement: e authors have nothing to disclose.

431

Distress in Patients with Non-Melanoma Skin Cancer

Caren Schierling 1; Andrea Forschner 2; Hans-Martin Häfner 2;

Stephan Zipfel 1; Andreas Stengel 1; Norbert Schäeler 1

1Universitätsklinikum Tübingen, Psychosomatische Medizin und

Psychotherapie, Tübingen, Deutschland

2Universitätsklinikum Tübingen, Universitäts-Hautklinik, Tübingen, Deutschland

Purpose: Non-Melanoma Skin Cancer (NMSC) is oen not regarded as

cancer by patients and considered less dangerous than malignant melano-

ma. Usually NMSC is treated curatively by surgical excision of the aected

area. So far, there is no reliable study examining the NMSC patient’s dis-

tress. e aim of this study was to examine the patient’s distress during the

oen several tumor surgeries to reach R0 resection.

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Methods: From 1/2018 to 2/2019 we examined N=168 inpatients at

the university skin clinic Tuebingen. To evaluate the distress, we used

Hornheider Screening Instrument (HSI), Patient-Health-Questionnaire

(PHQ-2), General Anxiety Disorder Screening (GAD-2), Distress er-

mometer (DT) and subjective need for support. Besides we used BFI-K

personality variables (based on the Big Five model) as possible predictors

and a self-developed questionnaire to investigate the patient’s awareness

of the disease. A diagnostic interview (based on QLQ-C30) and somatic

data from the clinical history completed the data collection. Follow-up

6 months aer the hospital-stay queried data on any changes of distress.

Results: Mean patient age was 62.9 years, 47.6% were female. e histo-

logically conrmed tumor type was in 79% (n1=133) basal cell carcinoma

and in 17% (n2=28) squamous cell carcinoma. In 68.4% tumor localiza-

tion was the facial area. e mean size of the largest operated defect was

5.5 cm². Patients with NMSC reported extremely low subjective support

needs (0.6%). Still, we identied an above-threshold value of DT in 46.1%.

In HSI 31.8% showed abnormal stress values, 11.7% indicated an anxiety

disorder (GAD-2) and 4.9% indicated depression (PHQ-2). Worries, anx-

ieties and sleep were most frequently mentioned in DT problem list.

Conclusions: Our data show that patients hardly express any subjective

need for psycho-oncological support, although a remarkable amount of

patients has increased distress levels. is could be due to the subjectively

lower threat attributed to NMSC. e follow-up was completed in 8/2019,

so that further results will be available at the congress.

566

Patientenkompetenz bei Krebspatienten: Welche Wirkung

haben Zeit seit Diagnose und eine kurative vs. palliative

Behandlungssituation?

Juergen M. Giesler 1; Joachim Weis 2

1Sektion Versorgungsforschung und Rehabilitationsforschung,

Universitätsklinikum Freiburg, Freiburg, Deutschland

2Stiftungsprofessur Selbsthilfeforschung, Tumorzentrum/CCC Freiburg,

Universitätsklinikum Freiburg, Freiburg, Deutschland

Purpose: Germany’s National Cancer Plan designates promoting Patient

Competence (PC) as one of its goals, while acknowledging a considerable

need of clarifying this concept itself and identifying potential determi-

nants and health-related outcomes. Against this background, we explored

potential eects of time since diagnosis (TSD) and a palliative treatment

situation on PC, coping self-ecacy, and quality of life.

Methods: In a study with three measurement points, we included 424

patients with breast, colorectal or prostate cancer in either oncological

rehabilitation or out-patient treatment (mean age 62 years, 53% female, 34%

under palliative treatment, median TSD 9.8 months). At each time point,

PC was measured with the Patient Competence Questionnaire 57 (PCQ-57)

that covers 8 PCs.1 To test for eects of TSD and treatment situation, we

computed 2 (TSD below median vs. TSD above median) x 2 (curative

vs. palliative treatment situation) ANOVAs on PC, coping self-ecacy

(CBI-B) and quality of life (QLQ-C30) as measured at baseline.

Results: Longer TSD was associated with signicantly stronger

competencies for seeking information, striving for autonomous decisions,

and using social benets, and also with better role functioning. Compared

to patients under curative treatment, patients under palliative treatment

reported dealing explicitly with the life-threat posed by cancer to a

signicantly larger extent. Also, they reported signicantly lower coping

self-ecacy and physical functioning. Eect sizes were generally small,

however.

Conclusions: e ndings suggest that a longer TSD and a palliative sit-

uation may independently impact on PC, coping self-ecacy and quality

of life. ey thus underline the need for supporting patients under these

conditions in their striving for autonomy and their coping eorts.

Reference:

1. Giesler JM, Weis J. Developing a self-rating measure of patient compe-

tence in the context of oncology: a multi-center study. Psychooncology.

2008;17(11):1089-1099.

Disclosure Statement: e authors have no conict of interest.

666

EPOS: Development and Evaluation of an Emotion-Based

Psychosocial Online Self-Help Program for Cancer Patients

Anna Mayer; Angeliki Tsiouris; Jörg Wiltink; Manfred E. Beutel;

Rüdiger Zwerenz

Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,

Universitätsmedizin Mainz, Mainz, Deutschland

Purpose: A cancer diagnosis is associated with considerable psychosocial

burdens and losses in quality of life. Many patients have problems to nd ad-

equate outpatient psycho-oncological help aer discharge from the clinic. In-

ternet-based interventions are regarded as a promising opportunity for can-

cer patients to overcome existing barriers to the use of psychosocial support

and to improve their psychological well-being, regardless of time or place.

Methods: Based on extensive literature research, focus groups with health

care professionals and interviews with cancer patients, we developed the

8-week online intervention epos (emotion-based psycho-oncological on-

line self-help). e program was designed for patients with all types of

cancer and follows the theoretical concepts of emotional mindfulness, re-

silience and positive psychology. It aims to reduce psychological distress

by (1) providing orientation and information (2) promoting their social

relationships and (3) strengthening their resilience.

Results: Epos includes an introductory module on mindfulness, followed

by seven modules on a specic psychosocial issue (e.g. talking about can-

cer, dealing with mental complaints, dealing with cancer in the social con-

text). Each module consists of psycho-educative elements as well as emo-

tion- or mindfulness-based exercises. Videos of ctional cancer patients

and psycho-oncological experts guide through the program.

Conclusions: With epos, an emotion-based online intervention has been

developed that complements conventional psycho-oncological treatment.

We assume that epos helps cancer patients to better cope with the major

psychological, social and physical challenges of the disease. In a random-

ized controlled trial (online self-help program + treatment as usual vs.

only treatment as usual) enrolling N=325 cancer patients, the ecacy and

acceptance of epos will be investigated.

Disclosure Statement: e authors declare no conict of interest.

695

Work Ability of Employed Cancer Survivors

Antonia Rabe 1; Elisabeth Jentschke 1; Tanja Bipp 2

1Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,

Würzburg, Deutschland

2Julius-Maximilians-Universität, Lehrstuhl für Psychologie II/ Arbeits-, Betriebs-

und Organisationspsychologie, Würzburg, Deutschland

Purpose: e aim of the study was to analyze work ability and its rela-

tionship with possible determinants, in particular with fatigue, occupa-

tional self-ecacy and job craing. It was examined, if self-ecacy and

job craing are helpful strategies to cope with fatigue at work and sustain

work ability.

Methods: A cross-sectional sample of individuals diagnosed with cancer

who nished primary treatment and have continued work lled out an

online questionnaire. Variables were assessed with common self-report

questionnaires. For consideration of the target group, a shortened version

of the Work Ability Index was used. Multiple regressions were executed

to examine associations while controlling for gender (female), working

hours and time since continuation of work. Additionally, participants

were asked which symptom was most hindering aer return to work.

Results: Participants (N = 69, female = 91.3%) were mostly diagnosed with

breast cancer (68.1%) and have reassumed work more than three years ago.

Fatigue was most frequently mentioned as a barrier aer return to work.

It was inverse related to general, physical and mental work ability. Women

and participants with a greater workload evaluated their work ability higher.

Moreover, participants with Fatigue reported a lower self-ecacy, but more

job craing. Job craing and self-ecacy did not moderate the relationship

between fatigue and work ability nor did job craing mediate it (p >.05).

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Conclusions: Quantitative and qualitative ndings implicate the burden

of fatigue at work. Employed cancer survivors suering from fatigue are

at risk to rate their work ability lower. Special attention should be directed

to mental work ability. e relevance of self-ecacy and job craing for

work ability should be investigated in larger studies.

Disclosure Statement: No conict of interest or nancial ties.

699

Distress Experiences and Acceptance of a Computer Based

Screening in Neuro-Oncological Patients

Jan Ilgen 1; Mirjam Renovanz 2; Stephan Zipfel 1; Andreas Stengel 1;

Norbert Schäeler 1

1Universitätsklinikum Tübingen, Abteilung für Psychosomatische Medizin und

Psychotherapie, Tübingen, Deutschland

2Universitätsklinikum Tübingen, Abteilung für Neurochirurgie, Tübingen,

Deutschland

Purpose: Psycho-oncological screening is mandatory for patient-cen-

tered care in oncology. is is challenging in neuro-oncology as motor

and mental dysfunctions are common.

From 2/2018 to 2/2019 we examined n = 100 patients who were in the

neurosurgical department of the University Hospital Tübingen for surgi-

cal tumor therapy. e aim of the study is to investigate the patient’s dis-

tress experiences as well as their individual stress factors and the feasibility

of a computer-based screening.

Methods: e Electronic Psycho-oncological Screening (ePOS) was used

to assess patient’s distress. It includes the Hornheider Screening Instru-

ment (HSI), Patient Health Questionnaire (PHQ-4), Distress ermome-

ter (DT) and a question assessing the subjective need for support. e Re-

siliency Scale (RS-13), the Helping Alliance Questionnaire (HAQ-S) and

the Barthel Index as an clinician reported outcome, were also surveyed.

Patients were assessed postoperatively by using a tablet. A follow-up mea-

surement is scheduled 6 months aer the rst measurement date and will

be completed by 9/2019.

Results: e average patient age was 52 years (SD:14). 53% of the patients

were female. Subjective need for psycho-oncological support was reported

by 21% of the patients. In DT 65% showed increased values. In the HSI,

34% had a need for psycho-oncological treatment. Indications of an anx-

iety disorder were found in 24% and depression in 19%. In RS-13 87%

showed moderate to high values. About 80% indicated the family doctor

as their outpatient primary care provider. Overall, 74% were able to han-

dle the tablet on their own.

Conclusions: Our data show that about every h neuro-oncological pa-

tient indicates a subjective need for psycho-oncological support. Outpa-

tient family doctors play the most important role in primary care. Overall,

there is a high acceptance of the electronic screening in the perioperative

situation.

741

The Need for Psycho-Oncological Support in Colorectal Cancer

Patients during dierent Treatment Phases

Ralf Reichelt

Onkotrakt AG, Hamburg, Deutschland

Purpose: Colorectal cancer is frequently associated with psychooncolog-

ical burden for the aected patients. Severity and temporal dimension are

oen not readily assessable.e aim of this study was to identify patients

in need of psychooncological support and to monitor these patients in the

long-term.

Methods: e present study was conducted in 25 German hospitals. 604

colorectal cancer patients were asked to answer the self-assessment Ques-

tionnaire on Stress in Cancer Patients – short form (Herschbach & Weis,

2010) [1] at least twice throughout the observation period.

Results: Among all colorectal cancer patients included, 35,6% suered

from psychooncological distress at the time of the rst survey. ere was

no signicant dierence between women (39,3%) and men (33,3%). e

average lead time between the rst and the second survey was 33,4 weeks.

94 patients completed at least the 2nd survey. During the second survey,

39,3% of the 28 initially burdened patients were still identied to require

psychooncological support. Among the 66 (70,2%) initially burden-free

patients, 78,8% still showed no psychooncological distress at the time

of the second survey. However, fourteen individuals out of this group

(21,2%) exhibited signicant signs of psychooncological impairment.

Conclusions: Psychooncological burden was observed in 35,6% of the

colorectal cancer patients at an early stage during the course of the dis-

ease and during the second survey in approximately 20% of all patients

who initially did not show any signs of psychological impairment. is

argues in favor that psychooncological burden may well occur in a small

but signicant subset of initially unaected colorectal cancer patients aer

a prolonged period of time.

Reference:

1. Herschbach, P., Weis, J. (Hrsg.) (2010). Screeningverfahren in der Psychoonko-

logie Testinstrumente zur Identikation betreuungsbedüriger Krebspatienten.

Eine Empfehlung der PSO für die psychoonkologische Behandlungspraxis,

Berlin 2010, 2. Auage

Disclosure Statement: ere is no conict of interest.

789

Inuence of a Rehabilitative Treatment after Resection of a

Benign Meningioma

Katharina Krause 1; Almuth F. Keßler 2; Ralf-Ingo Ernestus 2; Mario Löhr 2;

Elisabeth Jentschke 1, 3

1Universitätsklinikum Würzburg, Neurochirurgie, Neuropsychologie, Würzburg,

Deutschland

2Universitätsklinikum Würzburg, Neurochirurgie, Würzburg, Deutschland

3Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,

Psychoonkologie, Würzburg, Deutschland

Purpose: e BReMen Study (Belastung und Rehabilitation bei Meningeom-

patienten) concentrates on the (neuro)psychological burdens and limitations

of patients with benign meningiomas and examines which inuence a reha-

bilitation has and whether there is an indicator of when rehab is necessary.

Methods: In a prospective longitudinal trial, 80 patients with benign menin-

giomas will be examined over a period of 2 years. Test time points included

pre- (T1), post-surgery (T2), 3, 6, 12 and 24 months post-surgery.

In addition to sociodemographic data, localization/size of the menin-

gioma, use of rehabilitation and its duration, time of reintegration will be

recorded.

Questionnaires used to assess quality of life and aect: Short-Form

Health Questionnaire (SF-36), EORTC Quality of Life Questionnaire - C30,

EORTC QLQ for brain tumor patients, PHQ-9 depression score, GAD-7

general anxiety score and distress thermometer.

Neuropsychological tests used to examine cognitive functioning: Verbal-

er Lern- und Merkfähigkeitstest, Wechsler Memory Scale Revised, Regens-

burger Wortüssigkeitstest, Trail Making Test A+B, Stroop-Test and d2-R

Aufmerksamkeits- und Belastungstest.

Results: is interim analysis focused on PHQ-9, GAD-7 and distress levels.

So far, 61 patients were recruited, 23 dropped out. From 38 patients

which were examined one year post-surgery 80% claimed rehab.

While both groups show increased distress values, patients receiving re-

hab show an earlier distress decrease with lower long-term values.

Patients with higher depressiveness and anxiety have a stronger desire

for rehab; a medium-term drop of these values can be observed, followed by

a renewed increase to T5.

Conclusions: Increased depressiveness levels appear to be an indicator of

rehab need.

e stronger reduction of distress, depressivity and anxiety in the rehab

group indicate a positive rehab eect, while the later increase in depres-

siveness and anxiety levels seems to mark the need for further (neuro)

psychological care.

Disclosure Statement: No conicts of interest or nancial ties.

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842

A Clinical Trial of Group-Based Body Psychotherapy

to Improve Bodily Disturbances in Cancer Patients in

Combination with Randomized Controlled Smartphone-

Triggered Bodily Interventions – First Results

Astrid Grossert-Leugger 1, 2; Cornelia Meert 1; Viviane Hess 2, 3;

Christoph Rochlitz 2, 3; Miklos Pless 4; Sabina Hunziker 1, 3; Brigitta

Woessmer 5; Ulfried Geuter 6; Gunther Meinlschmidt 1, 3, 7, 8; Rainer Schäfert 1, 3

1Department of Psychosomatic Medicine, University Hospital Basel, Basel,

Schweiz

2Department of Medical Oncology, University Hospital Basel, Basel, Schweiz

3Faculty of Medicine, University of Basel, Basel, Schweiz

4Department of Medical Oncology, Winterthur Cantonal Hospital, Schweiz

5Outpatient practice for psychotherapy, Olten, Schweiz

6Institute for Sports and Motology, University of Marburg, Marburg, Schweiz

7Division of Clinical Psychology and Epidemiology Department of Psychology,

University of Basel, Basel, Schweiz

8Division of Clinical Psychology and Cognitive Behavioral Therapy , International

Psychoanalytic University, Berlin, Deutschland

Purpose: Disturbances in bodily well-being represent one key source of

suering and impairment related to cancer. ere is growing evidence that

body psychotherapy (BPT) is ecacious for the treatment of various men-

tal health problems. However, with regard to cancer patients, evidence is

scarce. Our aim was to evaluate whether group BPT can improve bodily

disturbances in post-treatment cancer patients.

Methods: Pre-post convergent parallel design of group BPT (6 weekly

sessions) using a waiting-period comparator, including a nested RCT:

During the BPT phase, either a smartphone-triggered bodily interven-

tion or a smartphone-triggered control intervention is provided at ran-

dom over 5 consecutive weeks, on 6 days weekly. Assessment took place at

three times (baseline, pre- and post-intervention), and on a daily basis for

the smartphone-triggered interventions. Inclusion criteria: Patients who

had received curatively intended treatment for any malignant neoplasm

(treatment being completed ≥3 months) and were suering from bodily

disturbances. Primary outcome: bodily disturbances assessed using the

‘Body Image Scale’. For the secondary outcomes standardized question-

naires are used to assess changes in experience of presence and vitality,

mood, body mindfulness, somatic symptoms and somatic symptom dis-

order, quality of life, anxiety, and depression including suicidal tendency,

vitality and mental health, as well as group cohesion.

Results: 171 patients were screened for eligibility; 40 patients attended the

group BPT and were randomized on a daily basis. 7 groups were conduct-

ed. Median age was 51.7 (22-77)y. 35 (87.5%) were female. 23 (57.5%) had

a malignant neoplasma of breast, 7 (17.5%) a lymphoma, 10 (25%) were

spread over various cancer types. Data analysis is ongoing at the time of

submission. First results will be presented at DKK.

Conclusions: Our trial has strong potential benets for cancer patients, as

it may introduce new therapeutic approaches to treat bodily disturbance

that persist despite curative tumor therapy.

Quality of Life

Poster

106

The Relationship between Posttraumatic Growth and Health-

Related Quality of Life in Adult Cancer Survivors: A Systematic

Review

Zhunzhun Liu; Daniela Doege; Melissa Thong; Volker Arndt

German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division of

Clinical Epidemiology and Aging Research, Heidelberg, Deutschland

Purpose: Studies reported dierent results on the relationship between

posttraumatic growth (PTG) and health-related quality of life (HRQOL)

in cancer survivors. is review aims to give an overview of current stud-

ies and to identify factors that potentially contribute to the heterogeneity

of the results on this topic.

Methods: is systematic review was registered in the International Pro-

spective Register of Systematic Reviews (ID: CRD42019121828), and con-

ducted and reported in accordance with PRISMA (Preferred Reporting

Items for Systematic Reviews and Meta-Analyses) guidelines. Eight litera-

ture databases were systematically searched using the concepts ‘posttrau-

matic growth’, ‘cancer’, and ‘health-related quality of life’. Eligible studies

(published until 2018) were reviewed, quality-assessed, and eect sizes

were extracted and synthesized.

Results: Of the 37 included articles, 22 received a rating of ‘weak’, 11 ‘mod-

erate’ and 4 ‘strong’ in study quality assessment. irty-ve independent

samples, mainly assessed in cross-sectional studies, were identied. e

overall sample comprised 7954 individuals, mean age of 55.3 years, >50%

females, predominantly breast cancer, and mainly focused on short-term

survivors (<5 years post-diagnosis). Variations in HRQOL measurement

and methodological inconsistency contributed to study-level dierences

of eect sizes. Sample-level factors were gender, cancer diagnosis, mean

age at study and geographic origin. Excluding studies of prostate cancer

survivors led to a decrease in heterogeneity regarding gender and diag-

nosis.

Conclusions: Studies assessing the relationship between PTG and

HRQOL were heterogeneous and results were dicult to combine. Over-

all, most studies found a positive relationship between the factors. How-

ever, studies of higher quality and longitudinal design are needed to better

understand the mechanisms behind that relationship, and to determine

whether PTG in cancer survivors can be modied by intervention in order

to improve HRQOL.

Disclosure Statement: None.

125

HELP (Heidelberger Entscheidungshilfen für Lungenkrebs-

Patienten) – Decision Aids for Lung Cancer Patients

Laura Unsöld; Nicole Deis; Anja Siegle; Corinna Jung;

Matthias Villalobos; Michael Thomas

Thoraxklinik Heidelberg, Onkologie der Thoraxtumoren, Heidelberg,

Deutschland

Purpose: Preference for patient participation increased over the past

30 years. Especially cancer patients with a limited prognosis have a strong

wish for information and participation. Decision aids (DA) are useful in-

strument to meet these needs. ey increase patients’ knowledge regard-

ing options and reduce decisional conicts. Benets of DA, relative to

usual care, are better knowledge of options, outcomes and more accurate

perceptions of outcome probabilities. Nonetheless, the use of DA by on-

cologists is still highly improvable. In the setting of limited prognosis that

comprises not only physical and psychosocial burden but also confronts

the patients and their relatives with an existential threat, many possible

barriers may hinder the adequate use of standardized aids. erefore the

aim of our project is the qualitative exploration, development and success-

ful implementation of DA for lung cancer patients.

Methods: 25 structured interviews with patients and their relatives will

be conducted regarding their wishes, needs and ideas in the decision

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making process. e healthcare-professionals perspective will be collected

through focus groups and all data will be analyzed with content analysis.

Based on these results and a thorough literature search, DA will be

developed and tested with the help of patient representatives. Aer a trial

period, the DA will be implemented in daily clinical practice following an

implementation plan. e success of the implementation will be measured

in the dimensions adherence and acceptance.

Results: Mainly focusing on the development of patient oriented DA and

their implementation rst preliminary results will be available up to the

time of the congress.

Conclusions: rough the integration of DA in clinical practice patients

and their family care-givers can be more actively involved in therapy- de-

cisions and patient’s competency and autonomy will be enhanced. e

implementation in daily clinical practice will be particularly challenging

as it also implicates dealing with important barriers perceived by the pro-

fessionals.

138

Prevalence and Intensity of Cancer-Related Fatigue Across a

Variety of Cancer Entities

Martina Schmidt 1; Silke Hermann 2; Karen Steindorf 1

1Division of Physical Activity, Prevention and Cancer, German Cancer Research

Center (DKFZ), Heidelberg, Deutschland

2Epidemiological Cancer Registry , German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

Purpose: To systematically assess and compare prevalence and intensity

of fatigue across the 16 most frequent cancer entities.

Methods: e FiX study enrolled cancer patients 1-2 years aer diagnosis

via the Epidemiological Cancer Registry of Baden-Württemberg. Fatigue

was assessed with the multidimensional EORTC QLQ-FA12 question-

naire. Age, sex, tumor and treatment data were derived from the cancer

registry. For calculating prevalence, patients with scores higher than the

age- and gender-specic 75th percentile from a representative sample of

the German general population were considered fatigued [1].

Results: A total of n=2,256 patients (50% male, 5% metastasized) with

a mean age of 66 ± 12 years were included in this analysis. e medi-

an (Q1, Q3) raw scores of physical fatigue ranged from 26.7 (13.3, 53.3)

among prostate and 33.3 (16.7, 66.7) among breast to 46.7 (26.7, 66.7) and

46.7 (26.7, 73.3) among stomach and pancreas cancer patients, respec-

tively. Prevalence was calculated for all fatigue dimensions and entities.

For example, physical fatigue was prevalent in 34% of prostate and 54%

of lung cancer patients. Aer adjusting for determinants of fatigue, i.e.

sex, age, BMI, type and timing of therapy, the intensity of physical fatigue

still diered among tumor entities (p = 0.018) with highest values among

patients with stomach, lung, pancreas, and kidney cancer and lowest val-

ues among patients with prostate and breast cancer. Breast cancer patients

also showed lowest adjusted levels of emotional fatigue.

Conclusions: Fatigue occurs across a large variety of cancer entities. In-

tensity and prevalence of fatigue in breast and prostate cancer patients

were in the lowest range among the 16 entities studied. As the majority

of observational and interventional research on fatigue is based on breast

cancer patients, the scope of this burdensome problem is probably not

fully ascertained.

Reference:

1. Hinz A, Weis J, Brähler E, Mehnert A. Fatigue in the general population:

German normative values of the EORTC QLQ-FA12. Qual Life Res.

2018;27:2681-2689

Disclosure Statement: none

226

Top 10 Living with and Beyond Cancer Research Priorities

Feng LI 1; Mariano Kalfors 1; Alexander Renziehausen 1; Patricia Ellis 2;

Stuart Griths 1; Ian Lewis 1; Ncri Lwbc Steering Group 3

1National Cancer Research Institute, London, United Kingdom

2James Lind Alliance, Southampton, United Kingdom

3https://www.ncri.org.uk/lwbc/about-psp/steering-group-and-partners/

Purpose: Currently 2.5 million people in the United Kingdom (UK) live

with a diagnosis of cancer and it is projected that by 2030 it will be over

four million [1]. Despite this, investment in research that aims to help

people live better with and beyond a cancer diagnosis has remained con-

sistently low and is currently only around 6% of UK cancer research spend

[3]. To address this, the 2015 National Health Service (NHS) England’s

Independent Cancer Taskforce report recommended identifying research

priorities on long-term patient needs and survivorship issues. Subse-

quently, the National Cancer Research Institute (NCRI), a partnership

of major cancer research funders, formed a Priority Setting Partnership

(PSP) with the James Lind Alliance to develop a list of priorities for Living

With and Beyond Cancer (LWBC) research.

Methods: e PSP had several stages, beginning with a UK-wide survey

to gather questions about uncertainties in living with and beyond cancer.

ese were further prioritized through an interim analysis and a second

survey before the top 10 list was decided during a nal stakeholder work-

shop. PSP participation was open to any adult rst diagnosed with can-

cer over the age of 16, their carers and health & social care professionals.

Questions on new cancer treatments solely aimed at extending life or only

relevant to end of life care were excluded.

Results: e rst survey had 1492 respondents who proposed 3500 unan-

swered questions and through an 18-month established rigorous process,

the questions were prioritized down to the Top 10 LWBC research priori-

ties (www.ncri.org.uk/lwbc).

Conclusions: is is the rst time that clear research priorities have been

identied in the UK to address questions that matter most to people af-

fected by cancer. e NCRI is working with funders, researchers, the NHS

and others to translate the priorities into research and patient benet, as

well as raise awareness of them internationally.

References:

1. Maddams J et al. (2012) BJC;107:1195–1202.

2. NCRI Cancer Research Database [Online, last accessed 18 March 2019].

Disclosure Statement: None

249

Impact Of Darolutamide (DARO) On Pain and Quality of Life

(QoL) in Patients (PTS) with Nonmetastatic Castrate-Resistant

Prostate Cancer (NMCRPC)

Tilman Todenhöfer 1; Karim Fizazi 2; Neal D. Shore 3; Teuvo Tammela 4;

Iris Kuss 5; Marie-Aude Le Berre 5; Ateesha F. Mohamed 5; Dawn Odom 6;

Jennifer Bartsch 6; Amir Snapir 7; Toni Sarapohja 7;

Matthew Raymond Smith 8

1Studienpraxis Urologie, Nürtingen, Deutschland

2Institute Gusta, University of Paris Sud, Villejuif, Frankreich

3Carolina Urologic Research Center, Myrtle Beach

4Department of Surgery, Tampere University Hospital, Tampere, Finnland

5Bayer AG, Berlin, Deutschland

6Research Triangle Institute, Durham, United States

7Orion Pharma, Orion Corporation, Espoo, Finnland

8Massachusetts General Hospital, Medicine, Boston, United States

Purpose: DARO is a structurally distinct androgen receptor antagonist

for which in vitro and phase 1/2 studies suggest low risk of adverse events

(AEs) and drug–drug interaction. In the ARAMIS study of DARO in

nmCRPC, metastasis-free survival (MFS) was signicantly prolonged vs

placebo (PBO) (40.4 vs 18.4 mo; hazard ratio [HR] 0.41; 95% condence

interval [CI] 0.34–0.50; P < 0.001) and interim overall survival (OS)

favored DARO (HR 0.71; 95% CI 0.50–0.99; P = 0.045).

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Methods: 1509 pts were randomized 2:1 to DARO 600 mg (two 300 mg

tablets) twice daily (n = 955) or PBO (n = 554) while continuing androgen

deprivation therapy (ADT). Primary endpoint was MFS. Secondary

endpoints included OS and time to pain progression. QoL was assessed

by EORTC-QLQ-PR25 at baseline (BL) and every 16 wks until end of

treatment. Analysis of time to deterioration (TTD) in EORTC-QLQ-PR25

subscales, dened as rst occurrence of a minimally important dierence.

Results: DARO signicantly delayed pain progression vs PBO (40.3 vs

25.4 mo; HR 0.65; 95% CI 0.53–0.79; P < 0.001); this was maintained be-

yond end of study treatment. TTD showed statistically and clinically sig-

nicant delays with DARO vs PBO for urinary symptoms (25.8 vs 14.8 mo;

HR 0.64; 95% CI 0.54–0.76; P < 0.01). TTD of hormonal treatment-related

symptoms was comparable with DARO vs PBO (18.9 vs 18.4 mo; HR 1.06;

95% CI 0.88–1.27; P = 0.52). DARO was well tolerated. Exposure-adjust-

ed incidences of AEs of interest were similar/lower with DARO vs PBO

(fatigue/asthenic conditions [11.3 vs 11.1], hypertension [4.7 vs 5.1], hot

ush [3.7 vs 4.1], fracture [3.0 vs 3.5], falls [2.7 vs 4.1], cognitive disorder

[0.3 vs 0.2], and seizure [0.2 vs 0.2]).

Conclusions: For nmCRPC pts, DARO prolongs MFS, is well tolerated,

maintains QoL, and delays worsening of pain and disease-related symp-

toms compared with PBO.

American Society of Clinical Oncology; Inc. Reused with permission. is abstract

was accepted and previously presented at the 2019 ASCO Annual Meeting. All

rights reserved.

Tilman Todenhöfer reports personal fees from Bayer Healthcare, Janssen, Astellas

outside the submitted work.

Karim Fizazi reports personal fees from Amgen, Astellas, Bayer, Clovis,

AstraZeneca, Janssen, Curevac, ESSA, Orion Pharma, Roche/Genentech, and

Sano outside the submitted work.

Neal D. Shore reports personal fees from Ferring, Bayer, Amgen, Janssen,

Dendreon, Tolmar, Astellas, Pzer, AstraZeneca, Genentech/Roche, Myovant

Sciences, Merck, AstraZeneca, Bristol Meyers Squibb, and Nymox outside the

submitted work.

Teuvo Tammela reports personal fees from Janssen, grants and personal fees from

Bayer, Lidds AB and Astellas, outside the submitted work.

Iris Kuss reports employment by and stock ownership in Bayer

Marie-Aude Le Berre is an employee of Bayer.

Ateesha F. Mohamed is an employee of Bayer.

Dawn Odom is a full time salaried employee of RTI Health Solutions. RTI Health

Solutions was retained by Bayer to conduct the analysis which is the subject of this

abstract.

Jennifer Bartsch is a full time salaried employee of RTI Health Solutions. RTI

Health Solutions was retained by Bayer to conduct the analysis which is the subject

of this abstract.

Amir Snapir reports personal fees from Orion Pharma during the conduct of the

study.

Toni Sarapohja reports to be an employee of Orion Corporation.

Matthew Raymond Smith reports personal fees from Amgen, Astellas, Bayer,

Clovis, Gilead, Janssen, Lilly, Novartis, and Pzer, outside the submitted work.

281

Association of Laparoscopic Colectomy Versus Open

Colectomy on the Long-Term Health-Related Quality of Life of

Colon Cancer Survivors

Melissa Thong 1; Lina Jansen 2; Jenny Chang-Claude 3;

Michael Homeister 2; Hermann Brenner 2; Volker Arndt 1

1DKFZ, Unit of Cancer Survivorship, Heidelberg, Deutschland

2DKFZ, Division of Clinical Epidemiology and Aging Research, Heidelberg,

Deutschland

3DKFZ, Division of Cancer Epidemiology, Heidelberg, Deutschland

Purpose: Laparoscopic colectomy (LC) is promoted as a less invasive al-

ternative to open colectomy (OC) in the treatment of stage I-III colon

cancer. Research on the long-term (5-years post-diagnosis) health-related

quality of life (HRQOL) of LC patients is scarce. Our study aimed to com-

pare the long-term HRQOL and psychological well-being of stage I-III

colon cancer survivors treated either with LC or OC.

Methods: is study used a German population-based cohort of 1066 pa-

tients who underwent either LC (n=86) or OC (n=980). LC patients were

matched to OC patients with a propensity score using a 1:2 nearest-neigh-

bor algorithm. e propensity score is derived from a set of baseline so-

ciodemographic, clinical, and lifestyle covariates. At 5-year follow-up,

patients completed assessments on HRQOL (EORTC-QLQ-C30 and

EORTC-QLQ-CR29) and psychological well-being (distress and disease/

treatment burden). Least square mean scores of HRQOL were derived us-

ing linear regression. Proportions of patients with moderate/high distress

and disease/treatment burden versus low were compared with chi-square

tests.

Results: In total, 81 LC patients could be matched to 156 OC patients.

More LC patients experienced disease progression (16% versus 7%,

p=0.02). On HRQOL, LC patients reported signicantly better body im-

age (87.1 versus 81.0, p=0.03) and generally less symptom burden, albeit

dierences were not signicant. Distress levels were generally low and

comparable between the two groups. OC patients were more likely to feel

moderate/high levels of burden associated with the treatment (72% versus

56%, p=0.01) and the time aer treatment completion (43% versus 28%,

p=0.02).

Conclusions: LC was associated with higher risk of disease progression

among stage I-III CRC patients, but LC patients reported comparable or

better long-term HRQOL outcomes and higher levels of psychological

well-being than OC patients 5 years aer diagnosis.

Disclosure Statement: No conict of interest declared.

289

Depression in Long-Term Breast Cancer Survivors Compared

to Female Population Controls in Germany: Age-Specic

Prevalence and Determinants

Daniela Doege 1; Melissa Thong 1; Lena Koch-Gallenkamp 2; Lina Jansen 2;

Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5; Ron Pritzkuleit 6;

Annika Waldmann 7, 8; Sylke Zeißig 9; Hermann Brenner 2, 10, 11; Volker Arndt 1

1German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division

of Clinical Epidemiology and Aging Research, Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and

Aging Research, Heidelberg, Deutschland

3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland

4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen

Cancer Registry, Bremen, Deutschland

5Saarland Cancer Registry, Saarbrücken, Deutschland

6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland

7Ministry of Health and Consumer Protection, Hamburg Cancer Registry,

Hamburg, Deutschland

8University Lübeck, Institute of Social Medicine and Epidemiology, Lübeck,

Deutschland

9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland

10German Cancer Research Center (DKFZ), Division of Preventive Oncology,

Heidelberg, Deutschland

11German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),

Heidelberg, Deutschland

Purpose: Depression is more prevalent in breast cancer (BC) patients

and survivors than in general population. However, little is known about

depression in (very) long-term survivors. e study objectives were (1)

to compare the age-specic prevalence of depressive symptoms (a) in BC

survivors vs. female population controls, (b) in disease-free BC survivors

vs. those who self-reported progression aer treatment vs. controls, and

(2) to explore determinants of depression in BC survivors.

Methods: 3010 BC survivors (stage I-III, 5-16 years post-diagnosis, mean

age 65 years at survey), and 1005 cancer-free population controls (mean

age 59 years) were recruited in German multi-regional population-based

studies. Depression was assessed by the short form of the Geriatric De-

pression Scale (GDS-15). Prevalence dierences between subgroups were

assessed via logistic regression, controlling for age and education. Multi-

nomial logistic regression was used to explore determinants of depression

in BC survivors.

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Results: A GDS-15 score suggestive of mild or severe depression (cut-o:

≥5) was found in 30.4% of BC survivors and in 23.8% of cancer-free con-

trols (p<0.0001), and a score suggestive of severe depression (cut-o: ≥10)

in 4.7% of BC survivors and 3.8% of controls (p=0.2107). At all ages <80

years, prevalence of mild/severe depression was signicantly higher in BC

survivors than controls, while at ≥80 years BC survivors showed lower

rates of severe depression than controls. BC survivors with progression

showed signicantly higher prevalence of mild/severe depression than

disease-free survivors and controls. Age, employment, income, partner-

ship, living situation and BMI were signicant predictors of depression

in BC survivors.

Conclusions: Long-term BC survivors <80 years report slightly but sig-

nicantly higher depression prevalence than controls, which might be

explained by disease progression. Clinicians should refer survivors to psy-

chological care when needed, especially in the case of disease progression.

Disclosure Statement: No conict of interest.

311

Validation of the Cancer Fatigue Scale in a Geriatric

Population

Anne-Kathrin Klaus 1, 3, 4; Roland Zerm 1, 3; Anette Mehl 3;

Thomas Ostermann 2, 5; Daniela Rodrigues Recchia 5; Marcus Reif 6;

Hans Broder von Laue 3; Benno Brinkhaus 4; Matthias Kröz 1, 2, 3, 4

1Hospital Havelhöhe, Internal Medicine, Berlin, Deutschland

2Witten/ Herdecke University, Integrative Medicine, Witten, Deutschland

3Research Institute Havelhöhe, Berlin, Deutschland

4Charité University, Institute for Social Medicine, Epidemiology and Health

Economics, Berlin, Deutschland

5Witten/ Herdecke University, Methodology and Statistics in Psychology and

Psychotherapy, Witten, Deutschland

6Society for Clinical Research, Berlin, Deutschland

Purpose: Cancer related Fatigue (CRF) is a burdensome symptom both

generally and particularly in geriatric cancer patients. A variety of validat-

ed questionnaires exist to assess CRF, either unidimensional, e.g. Function-

al Assessment of Chronic Illness erapy-Fatigue or multidimensional,

e.g. Multidimensional Fatigue Inventory or the Cancer Fatigue Scale

(CFS-D). e CFS-D is validated in German for cancer patients from 30

to 83 years with robust validity. Since there is no validation specically

for a geriatric population older than 83 years we conducted this geriatric

validation study.

Methods: Reliability of the CFS-D has been assessed by Cronbach-α, and

test-retest reliability (with a test-retest time-span of 2–4 weeks) by Spear-

man rank correlation. Additionally, a factor analysis and a structural equal

modeling (SEM) has been conducted. e cumulative illness rating scale

(CIRS), physical self-maintenance scale (PSMS), geriatric depression scale

(GDS), sleep quality (DGSM), health-related quality of life (SF-12), Kar-

nofsky performance index (KPI) and actigraphy have been recorded as

external validity criteria.

Results: We included 104 participants between 70 and 96 years (31 cancer,

22 diabetes mellitus type 2, and 51 age-matched comparatively healthy

controls. e 15-item CFS-D questionnaire revealed good internal con-

sistency (Cronbach’s-α r = 0.88) and satisfying test-retest reliability (r =

0.68). Concordant construct and convergent validity with correlations

to CIRS, PSMS, GDS, SF-12 and actigraphical rest/activity rhythm vari-

ability were documented (r = 0.28–0.49, all p<0.05). e factor analysis

revealed a 3-factor structure. Although the subscales diered in item load-

ing from the published CFS-D the SEM conrmed the initial validation

subscales structure (physical, cognitive, aective fatigue) to be robust and

usable for a geriatric sample.

Conclusions: e Cancer Fatigue Scale (CFS-D) is a reliable and valid

questionnaire to measure fatigue up to 96 years, however subscale dier-

ences demand clarication for highly aged individuals.

441

Inuencing Factors on the Development of Physical

Functioning of Older Cancer Patients During and 12 months

After Cancer Therapy - A Prospective Observational Study

Johannes Kooymann 1; Stephanie Witte 1; Daniel Medenwald 2;

André Golla 3; Gabriele Stangl 4; Anke Steckelberg 1; Dirk Vordermark 2;

Heike Schmidt 1

1Institute of Health and Nursing Science, Medical Faculty of Martin Luther

University Halle-Wittenberg, Halle (Saale), Deutschland

2University Clinic and Outpatient Clinic for Radiotherapy, Medical Faculty of

Martin Luther University Halle-Wittenberg, Halle

3Institute of Rehabilitation Medicine, Medical Faculty of Martin Luther

University Halle-Wittenberg, Halle

4Institute for Agricultural and Nutritional Science, Martin Luther University

Halle-Wittenberg, Halle

Purpose: is study aims to generate hypotheses regarding modiable

factors associated with the development of physical function of older can-

cer patients undergoing cancer therapy.

Methods: Exploratory, prospective observational study including cancer

patients ≥65 years treated with radiotherapy. Assessments of ADL, IADL,

physical function (TUG, handgrip, 6 min. walk test), physical activity

(PASE), nutritional status, cognition (minicog), depressed mood (PHQ9),

social situation and health-related quality of life (EORTC QLQ-C30,

ELD14) at baseline (t0), 6 (t2) and 12 months (t4); postal assessments at 3

(t1) and 9 months (t3). Descriptive analyses included Spearmans Rho (rs)

to examine associations between the EORTC QLQ-C30 subscale physical

function (PF) and possible inuencing factors.

Results: Forty patients, mean age 74.4 ±5.3 years, n=24 male, participated.

Analyses show a clinically relevant change of PF over time (Ø t0: 79.8 ±8.1;

Ø t1: 63.6 ±26.9; Ø t2: 65.0 ±26.7; t3: ø 60.8 ±25.7; t4: ø 61.7 ±34.0). Data

show correlations of albumin (t0) with PF (t2) (rs=0,446) and depressed

mood PHQ9 (t0) with decreased PF at t2 (t2: rs=-0,486). At 12 months

the correlation of PHQ9 (t4) with PF (t4) is stronger (t4: rs=-0.532) than

the correlation of the EORTC QLQ-C30 subscale emotional function with

PF (rs=0,526). Out of the objective assessments, baseline TUG shows the

strongest correlation with PF at t2 and t4 (t2: rs=-0.523; t4 rs=-0.605).

Conclusions: While 6 months data indicate that baseline mental health

and good nutritional status are associated with the maintenance of physi-

cal function, at 12 months mental health shows the strongest association.

Aiming for targeted interventions, these hypotheses should be examined

in further studies.

Disclosure Statement: e authors do not have any conicts of interest relevant to

the topic to declare.

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445

AML Survivorship – Somatic and Psychosocial Long-Term

Eects of AML Therapy

Eva Telzerow 1, 2; Maria Christina Sauerland 3; Maja Rothenberg-Thurley 2;

Friederike Mumm 2; Jan Braess 4; Bernhard Wörmann 5; Utz Krug 6;

Wolfgang E. Berdel 7; Michael von Bergwelt-Baildon 2;

Wolfgang Hiddemann 2; Karsten Spiekermann 2; Pia Heußner 2, 8;

Dennis Görlich 3; Klaus Metzeler 2

1Psycho-Oncology, Comprehensive Cancer Center, Ludwig-Maximilians-

University Munich, Munich, Deutschland

2Department of Internal Medicine III, Ludwig-Maximilians-University Munich,

Munich, Deutschland

3Institute of Biostatistics and Clinical Research, Westfälische Wilhelms-

Universität Münster, Münster, Deutschland

4Department of Oncology and Hematology, Hospital Barmherzige Brüder,

Regensburg, Deutschland

5Charité University Hospital Berlin, Berlin, Deutschland

6Hospital Leverkusen, Leverkusen, Deutschland

7Deparment of Medicine A, Westfälische Wilhelms-Universität Münster, Münster,

Deutschland

8Hospital Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland

Purpose: An increasing proportion of patients with Acute Myeloid Leu-

kemia (AML) become long-term survivors. Somatic and psycho-social

outcomes are therefore becoming increasingly important, but little is

known about the long-term eects of the disease and its treatment. We

therefore designed a comprehensive analysis of AML survivorship out-

comes on multiple levels: somatic health status, psycho-social well-be-

ing, and genetics (clonal hematopoiesis). ese data will aid in designing

risk-adapted follow-up programs for long-term survivors.

Methods: We are including adult AML patients who were enrolled in

AML-CG multicenter trials (AML-CG 1999, AML-CG 2004 and AML-

CG 2008) or in the AML-CG patient registry, and who are alive and in

remission ≥5 years aer their initial diagnosis. Eligible patients receive a

14-page questionnaire with standardized instruments addressing dierent

relevant aspects of survivorship, including quality of life, life satisfaction,

fatigue, somatic health status and socio-economic status. e results will

be compared to data from age-matched healthy adults to assess the impact

of past AML therapy on various domains of well-being.

In a second step, we are also asking patients to also provide a periph-

eral blood sample, aiming to study leukemia-associated or treatment-in-

duced genetic alterations in long-term survivors. We will use these genet-

ic data to study associations between treatment regimens (e.g. allogeneic

transplantation), clonal hematopoiesis, and relevant long-term health out-

comes such as cardiovascular disease.

Results: 820 eligible potential participants have been identied. In a fea-

sibility study, 102 of 200 persons (51%) responded to the rst invitation

to participate. Enrollment is ongoing, and we expect to obtain data from

approximately 400 former AML patients. First results on recruitment and

descriptive analysis of relevant aspects on survivorship will be presented

at the meeting.

Conclusions: We will present an ongoing study of long-term health out-

comes in AML survivors.

448

Health-Related Quality of Life (HRQOL) Reported by Patients

with Multiple Myeloma (MM) in Germany

Monika Engelhardt 1; Gabriele Ihorst 2; Moushmi Singh 3; Martina Schöhl 4;

Achim Rieth 4; Grece Saba 5; Marine Pellan 5; Andrea Lebioda 4

1University Hospital Freiburg, Klinik für Innere Medizin, Klinik für Tumorbiologie,

Freiburg, Deutschland

2University Medical Center Freiburg, Freiburg im Breisgau, Deutschland

3Amgen, Denham, United Kingdom

4AMGEN GmbH, München, Deutschland

5Kantar, Paris, Frankreich

Purpose: Patient-focused care is the key to optimal management of

multiple myeloma (MM). Novel treatment options have improved life

expectancy, but real-world data on health-related quality of life (HRQoL)

is still scarce. Here, we report HRQoL of patients with MM by number of

treatment lines in real-world clinical practice in Germany.

Methods: An observational, cross-sectional, multicenter study was con-

ducted in 2019 to assess overall QoL global health status (GHS), function-

al capacity, and symptoms using the validated European Organization for

Research and Treatment of Cancer (EORTC) Core Quality of Life ques-

tionnaire (QLQ-C30) and the Quality of Life Multiple Myeloma module

(QLQ-MY20). For bivariate analyses, Student´s t-tests or one-way anova

were used, while Pearson´s chi-squares were applied for categorical vari-

ables. For subgroup analyses multivariate analyses have been used. Miss-

ing values have been excluded from the analyses.

Results: In total, 490 myeloma patients from 40 German centers were en-

rolled. e care setting included oce-based practitioners (43%), cancer

centers (25%), hospitals (23%) and university hospitals (10%). Median age

of patients was 72 years and 62% were male. At study participation, 71%

of patients were actively treated. Over a third (35%) had a previous stem

cell transplantation. Most (77%) patients had ≥1 comorbidity. Mean (stan-

dard deviation [SD]) EORTC QLQ-C30 GHS scores decreased from 61.7

(19.3) in 1st line (n=101) to 46.3 (19.4) in 4th line (4L) or later (n=97). e

mean dierence in GHS scores was 6.4 between 2nd and 3rd line and was

the highest (15.3) between supportive care and 4L. In all functional and

symptom scales, HRQoL was worsening as the number of treatment lines

increased. Similar results were found using EORTC QLQ-MY20 scales.

Conclusions: e observed HRQoL deterioration in later versus earlier

lines, stresses the importance of maintaining HRQoL for as long as pos-

sible. As age, remission, comorbidities and therapy are interacting with

HRQoL, further HRQoL analyses are needed to determine how to pre-

serve QoL of MM patients.

Conicts of Interest:

M. Engelhardt: ME has received educational and trial support from Amgen,

Celgene, Takeda, BMS, Janssen, Novartis, Karyopharm, and has received honoraria

and consultancy fees from BMS, Celgene, Amgen, Takeda, Novartis and Janssen.

G. Ihorst has received consultancy fees from Amgen.

G. Saba and M. Pellan are employees of Kantar Health who received funding from

Amgen to conduct this research.

A. Rieth, M. Schoehl and A. Lebioda are employees of Amgen GmbH and hold

Amgen stocks.

M. Singh is an employee of Amgen Ltd. Uxbridge.

489

Development of Tumor Disease-Specic PRO-CTCAE Item Sets

Maximilian Günther 1; Markus Schuler 2; Leopold Hentschel 3;

Katharina Schütte 3; Yon-Dschun Ko 4; Ingo Schmidt-Wolf 5; Ulrich Jaehde 1

1Clinical Pharmacy, University of Bonn, Bonn, Deutschland

2Department of Oncology, Helios Hospital Emil von Behring, Berlin,

Deutschland

3University Cancer Centre, University Hospital Carl Gustav Carus, Dresden,

Deutschland

4Department of Internal Medicine, Johanniter Hospital, Bonn, Deutschland

5Department of Integrated Oncology, University Hospital, Bonn, Deutschland

Purpose: In oncology, adverse events (AE) are mainly documented

using the Common Terminology Criteria for Adverse Events (CTCAE)

(1). is physicians’ assessment can be supported by patient-reported

outcomes (PRO) (2). For this reason, the NCI has developed a PRO

version of the CTCAE criteria, consisting of a pool of 78 symptoms

and 124 items (3). A core item set containing 31 items for patients with

chemotherapy has already been validated in German (4). e aim of this

study was to develop tumor disease-specic PRO-CTCAE item sets for

dierent tumor entities with high content validity.

Methods: Patients treated at three outpatient centres were asked to assess

the occurrence and relevance of the 78 PRO-CTCAE symptoms using

a questionnaire. In order to select PRO-CTCAE items for each tumor

entity, individual symptoms were ranked on the basis of occurrence and

relevance.

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Results: In the nal evaluation 101 patients with breast cancer with and

without metastases (BC) and 107 patients with multiple myeloma (MM)

were analysed. e BC item set contains 39 items representing 21 symp-

toms, the MM item set 39 items for 19 symptoms. 32 items for 16 symp-

toms are included in both item sets. Four out of the ve main symptoms

with the highest raking in both item sets were fatigue, numbness and tin-

gling, sleep disorders and nausea. e symptom with the highest ranking

included only in one item set was blurred vision in the BC item set and

anxiety in the MM item set. 24 items of the core item set were included in

the MM item set, 17 items in the BC item set.

Conclusions: Based on patient-reported dierences in symptom pattern,

specic PRO-CTCAE item sets with high content validity were developed

for breast cancer and multiple myeloma. eir psychometric criteria will

be analysed in a validation study.

References:

1. NCI. CTCAE Version 5.0. 2017

2. Basch E. N Engl J Med 2010; 362: 865-869

3. Basch E et al. J Natl Cancer Inst 2014; 106: 1-11

4. Hagelstein V et al. Ann Oncol 2016; 27: 2294-2299

Disclosure Statement: e authors do not have to disclose any conicts of interest.

570

Late Toxicities and Long-Term Health-Related Quality of Life

Among Head and Neck Cancer Survivors

Katherine Taylor 1; Cecilie Delphin Amdal 2; Guro Lindviksmoen Astrup 3;

Kristin Bjordal 4; Andreas Böhm 5; Bente Brokstad Herlofson 6, 7;

Ayman Bushnak 8; Joaquim Castro Silva 9; Alexander Fabian 10;

Johanna Inhestern 11; Ulrike Mölle 5; Michaela Plath 12; Susanne Singer 13

1Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz,

Deutschland

2Oslo University Hospital, Oncology Department, Oslo, Norwegen

3Oslo University Hospital, Department of Oncology / Research Support Service,

Oslo, Norwegen

4Oslo University Hospital, Institute for Clinical Medicine, Oslo, Norwegen

5St. Georg Hospital, Department of Otolaryngology, Head and Neck Surgery,

Leipzig, Deutschland

6Oslo University Hospital, Unit of Oral and Maxillofacial Surgery, Department

of Otorhinolaryngology - Head and Neck Surgery Division of Head, Neck and

Reconstructive Surgery, Oslo, Norwegen

7Oslo University, Faculty of Dentistry, Oslo, Norwegen

8University Hospital Giessen, Department of Otolaryngology, Head and Neck

Surgery, Giessen, Deutschland

9Instituto Português de Oncologia Francisco Gentil do Porto, Department of

Otolaryngology, Head and Neck Surgery, Porto, Portugal

10University Hospital Schleswig-Holstein, Radiation Therapy Department, Kiel,

Deutschland

11Oberhavel Hospital, Department of Otolaryngology, Head and Neck Surgery,

Henningsdorf, Deutschland

12University Hospital Heidelberg, Department of Otolaryngology, Head and

Neck Surgery, Heidelberg, Deutschland

13University Hospital Mainz, Institute for Medical Biostatistics, Epidemiology and

Informatics, Mainz, Deutschland

Purpose: To measure the health-related quality of life (HRQoL) and ex-

tent of treatment- and disease-related toxicities in head & neck cancer

(HNC)survivors more than 5 years’ post-treatment. e main research

questions aim to examine HRQoL dierences between the survivors and

reference HNC patient data from before treatment and 1 year post-treat-

ment and to observe the frequency of toxicities among the survivors.

Methods: In this on-going, cross-sectional study coordinated by the

University Hospital in Mainz, Germany, collaborators from 16 countries

invite eligible survivors to their clinic, where they undergo a clinical ex-

amination for toxicities (measured with the CTCAE) and ll out ques-

tionnaires on HRQoL, productivity losses, use of medical services, and

supportive care needs. is project began in September 2017 and will run

until October 2021.

Results: To date, questionnaires have been robustly translated into 11 lan-

guages and ethical approval obtained at more than 10 sites. 214 survivors

have been enrolled by 8 sites in 4 countries, with 5 more countries (7 new

sites) expected to begin enrolment during fall 2019. Project meetings have

taken place 4 times a year since the fall of 2017.

Conclusions: is project is progressing well and will provide compre-

hensive information on the long-term problems survivors deal with and

which HRQoL issues appear to improve or worsen. Examples of frequent

problems among long-term survivors include dry mouth, dysphagia, so

tissue brosis, and peripheral sensory neuropathy. An international ef-

fort provides an opportunity to enroll a large cohort of long-term HNC

survivors using standardized instruments. To date, studies on long-term

eects have oen included relatively few survivors, largely limited to sin-

gle countries.

Disclosure Statement: Nothing to disclose.

680

Impact of Oncological Therapy and Viscum Album

L. Treatment on Health Related Quality of Life in Breast

Cancer Patients

Shiao Li Oei 1; Anja Thronicke 1; Matthias Kröz 1, 2, 3; Philipp von Trott 4;

Harald Matthes 1, 4, 5; Friedemann Schad 1, 4

1Research Institute Havelhöhe, Berlin, Deutschland

2Institute of Social Medicine, Charité Universitätsmedizin Berlin, corporate

member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin

Institute of Health, Berlin, Deutschland

3Institute for Integrative Medicine, Universität Witten/ Herdecke, Witten,

Deutschland

4Interdisciplinary Oncology and Palliative Care, Hospital

Gemeinschaftskrankenhaus Havelhöhe, Berlin, Deutschland

5Institute of Social Medicine, Epidemiology and Health Economics and

Medical Department of Gastroenterology, Infectiology and Rheumatology,

Charité Universitätsmedizin Berlin, corporate member of Freie Universität

Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,

Deutschland

Purpose: Viscum album L. extracts (VA) are frequently used in integrative

oncology to enhance health-related quality of life (HRQL). e key im-

plication of this study was to evaluate the impact of oncological therapies

and add-on VA applications on HRQL in breast cancer patients.

Methods: Clinical and demographic data were retrieved from the Net-

work Oncology cancer registry. Primary non-metastasized breast cancer

patients treated with oncological standard therapy alone or in combina-

tion with VA-applications were included. At rst diagnosis and 24 months

later the European Organization of Research and Treatment Health-Relat-

ed Quality of Life Core Questionnaire (EORTC-QLQ-C30) were admin-

istered and evaluated.

Results: A total of 118 patients (median age 60 years) received standard

oncological therapy, 85 patients of them (72%) endocrine therapy, 34

(29%) chemotherapy (Ctx), and 12 (10%) immunotherapy. 49 patients

(42%) received additionally VA applications. Adjusted multivariable lin-

ear regression analyses revealed for the study cohort that Ctx, immuno-,

and endocrine therapies had a worsening of 17, 17, and 6 point changes

respectively for fatigue, while VA applications showed an improvement

of 12 point change (p = 0.0004). A similar impact of worsening (standard

oncological treatment regimens) and improvement (add-on VA) on in-

somnia (p = 0.009) and physical functioning (p = 0.005) were observed.

Conclusions: In the present longitudinal real-world observational anal-

ysis Ctx, immuno-, and endocrine therapies showed a negative impact

while add-on VA applications in addition to standard therapy had a sup-

portive eect on HRQL. us, add-on VA applications might be suited

to partially alleviate discomfort symptoms during anticancer strategies in

breast cancer patients.

Disclosure Statement: Grants from Helixor Heilmittel GmbH, Iscador AG and

ABNOBA GmbH (FS). Lecturer Honorarium from Helixor Heilmittel GmbH

(MK). No competing interests (SLO, AT, PT, HM).

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The Electronic Assessment of Patient-Reported Outcomes and

Quality of Life in Radiooncology – Pilot Implementation and

Process Evaluation

Thomas Nordhausen 1; Dirk Vordermark 2; Bernhard Holzner 3, 4;

Haifa Kathrin Al-Ali 5, 6; Gabriele Meyer 1; Heike Schmidt 2, 7

1Institute of Health and Nursing Science, Martin Luther University Halle-

Wittenberg, Deutschland

2Department of Radiation Oncology, University Hospital Halle (Saale),

Deutschland

3Department of Psychiatry, Psychotherapy and Psychosomatic Medicine,

University Hospital Innsbruck, Österreich

4Evaluation Software Development, Österreich

5Department of Internal Medicine IV, University Hospital Halle (Saale),

Deutschland

6Krukenberg Cancer Center, University Hospital Halle (Saale), Deutschland

7Institute of Health and Nursing Science, Martin Luther University Halle-

Wittenberg, Halle (Saale), Deutschland

Purpose: Numerous studies have shown the benet of Patient-Reported

Outcome measurements (PROM) including Health Related Quality of

Life (HRQOL) in clinical practice. However, standardized assessments are

still not part of clinical routine. A successful implementation in clinical

practice needs a structured approach including participation of all stake-

holders/parties involved as well as understanding of clinical practice, re-

quired changes, process evaluation and training.

Methods: 1. Analysis of current practice, assessment of facilitators and

barriers of implementation; 2. Interprofessional focus groups to decide on

PROMs, assessment times and clinical pathways; 3. Development of face

to face training and e-learning for clinical sta; 4. Stepwise implementa-

tion for in-patients and out-patients; 5. Process evaluation and optimiza-

tion; 6. Evaluation of impact.

Results: e still ongoing project is currently in phase 4. Sta decided on

initial assessment of HRQOL (EORTC QLQ C30) followed by daily mon-

itoring of a core set of eleven symptoms combined with few site specic

questions based on EORTC single items and a nal assessment of HRQOL

at the end of the treatment. Developed guidelines how to react to symp-

toms are accessible for clinicians to ensure quality of care and to facili-

tate communication with patients. e electronic questionnaires are well

accepted by patients and facilitate documentation and allocation of sup-

portive measures. Process evaluation shows, that time, interprofessional

communication and continuous support is needed to achieve changes of

clinical routine. Support by clinic IT is crucial to guarantee success.

Conclusions: e integration of the electronic assessment of HRQOL

into clinical practice is facing some challenges due to the complexity of

the implementation process. A manual based on the results of the process

evaluation, consisting of the many aspects that have to be considered, can

support further implementations in other oncological settings.

Disclosure Statement: Bernhard Holzner holds IPRs on the PROM soware

CHES.

792

Health-Related Quality of Life and Psychosocial Well-Being in

Cancer Survivors >10 Years Past Diagnosis

Daniela Doege 1; Melissa Thong 1; Linda Weißer 2; Lena Koch-Gallenkamp 2;

Lina Jansen 2; Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5;

Ron Pritzkuleit 6; Annika Waldmann 7; Sylke Zeißig 8; Hermann Brenner 2, 9, 10;

Volker Arndt 1

1German Cancer Research Center (DKFZ), Unit of Cancer Survivorship, Division

of Clinical Epidemiology and Aging Research, Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and

Aging Research, Heidelberg, Deutschland

3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland

4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen

Cancer Registry, Bremen, Deutschland

5Saarland Cancer Registry, Saarbrücken, Deutschland

6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland

7Ministry of Health and Consumer Protection, Hamburg Cancer Registry,

Hamburg, Deutschland

8Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland

9German Cancer Research Center (DKFZ), Division of Preventive Oncology,

Heidelberg, Deutschland

10German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),

Heidelberg, Deutschland

Purpose: Little is known about health-related quality of life (HRQoL) in

very long-term cancer survivors >10years past diagnosis. It is of great

interest, whether these survivors’ HRQoL diers from that of the gener-

al population and to which extent cancer still plays a role in their lives.

Study objectives were (1) to compare cancer survivors’ HRQoL to that

of non-cancer controls, and (2) to assess the prevalence of (a) fear of re-

currence (FoR), (b) cancer burden, and (c) the self-identity of still being

a cancer patient.

Methods: e samples of 2713 breast, colorectal and prostate cancer sur-

vivors (13–23years post-diagnosis) and 1765 controls were recruited in

German multi-regional population-based studies. HRQoL was assessed

by the European Organization for Research and Treatment of Cancer

Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Dierences

in HRQoL were assessed with multiple regression, controlling for age and

education. FoR was assessed with PAF-KF (Progredienzangst-Fragebogen

Kurzform). Patient identity and cancer burden were assessed by single

item questions.

Results: Cancer survivors’ overall QoL/ global health status was slightly

higher than that of same-age general population and they reported less

pain. However, they perceived a slightly lower social function, and more

dyspnea, constipation, and diarrhea. 12% of cancer survivors reported

high FoR (moderate fear: 19%). Although 75% reported that their treat-

ment had ended, 17% of those still felt as a cancer patient. A low, moderate

or high burden of the cancer on their current lives was reported by 46%

of all survivors.

Conclusions: Most functioning aspects of very long-term cancer sur-

vivors were comparable to same-age population controls. A majority of

cancer survivors reported a low FoR and a small symptom burden. How-

ever, even many years aer end of treatment, cancer-related symptoms

and fears still play a role in survivors’ lives. e need of continuous care

aer the end of regular treatment, including psychosocial aspects, seems

to be warranted.

Disclosure Statement: No conict of interest.

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803

Health-Related Quality of Life in Long-Term Survivors of

Metastatic Cancer

Volker Arndt 1; Lena Koch-Gallenkamp 2; Daniela Doege 1; Melissa Thong 1;

Heike Bertram 3; Andrea Eberle 4; Bernd Holleczek 5; Ron Pritzkuleit 6;

Annika Waldmann 7, 8; Sylke Zeißig 9; Lina Jansen 2; Hermann Brenner 2, 10, 11

1Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging

Research, German Cancer Research Center (DKFZ), Heidelberg, Deutschland

2Division of Clinical Epidemiology and Aging Research, German Cancer

Research Center (DKFZ), Heidelberg, Deutschland

3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland

4Bremen Cancer Registry, Leibniz Institute for Prevention Research and

Epidemiology - BIPS, Bremen, Deutschland

5Saarland Cancer Registry, Saarbrücken, Deutschland

6Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland

7Hamburg Cancer Registry, Ministry of Health and Consumer Protection,

Hamburg, Deutschland

8Institute of Social Medicine and Epidemiology, University Lübeck, Lübeck,

Deutschland

9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland

10Division of Preventive Oncology, German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

11German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),

Heidelberg, Deutschland

Purpose: e challenges of cancer survivors have gained increasing at-

tention in recent years. However, most pertinent publications focused on

survivors with cancer in remission. In contrast, long-term survivors with

metastatic cancer have not been well studied. In this study, we describe

health related quality of life (HRQoL) in long-term survivors aer diag-

nosis of metastatic cancer in comparison to non-metastatic survivors and

population controls.

Methods: 6952 long-term cancer survivors (5-16 years past diagnosis

of breast [n=3045], colorectal [n=1504], or prostate cancer [n=2403]),

recruited in the population-based CAESAR + study, were compared ac-

cording to tumor stage with 1878 cancer free controls from the German

general population. Stage at diagnosis could be classied into localized

[n=3984], regional [n=1821], and localized disease [n=129] in 5934 cancer

survivors. HRQoL was assessed by the EORTC QLQ-C30. e association

between tumor stage and HRQoL was analyzed using multiple regression

while controlling for age, gender, and education. Supplemental analyses

were employed to assess the impact of disease recurrence on HRQoL.

Results: Long-term survivors with distant disease reported signicantly

poorer global health and quality of life across multiple dimensions includ-

ing physical, role, and social functioning and more nancial diculties

and symptoms such as fatigue, insomnia, and dyspnea than survivors with

regional metastases or localized disease as well as population controls (all

p< 0.01). Recurrence of disease occurred more oen among survivors

with distant cancer (36%) than among survivors with regional (17%) or

localized disease (11%) and was strongly associated with poorer HRQOL.

However, recurrence of disease did not fully explain the detriments in

HRQOL in survivors with distant cancer.

Conclusions: Cancer survivors with either metastatic disease or disease

recurrence suer in particular from long-lasting detriments in HRQoL.

e experience of these survivors should not be neglected in cancer sur-

vivorship research.

813

Adolescents and Young Adults are at Risk for Psychosocial

Sequelae after Cancer Treatment

Andreas Wittwer 1; Peter Kropp 2; Kristin Pulewka 3; Andreas Hochhaus 1;

Inken Hilgendorf 1

1Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische

Onkologie, Universitätsklinikum Jena, Jena, Deutschland

2Institut für Medizinische Psychologie und Medizinische Soziologie,

Universitätsmedizin Rostock, Rostock, Deutschland

3Institut für Psychosoziale Medizin und Psychotherapie, Universitätsklinikum

Jena, Jena, Deutschland

Purpose: Adolescents and young adults (AYA) who survive cancer are at

high risk for psychological and social sequelae. Aiming to explore unmet

needs and psychosocial distress, we performed a survey among all AYA

treated for a haematological malignancy at our center since January 2010.

Methods: 85 AYA-survivors were invited to join the survey; at median

of 36 (2-86) months aer completion of therapy. A set of standardized

screening instruments for psychosocial stressors (PhQ-S), symptoms of

depression (PHQ-9), generalized anxiety (GAD7), fear of progression

(PAF-KF), quality of life (EORTC QLQ-C30) and a self-designed ques-

tionnaire were sent to the patients.

Results: Data from a total of 47 (20 male) patients were available. Median

age was 35 years. e mean on all QLQ-C30 function scales was less than

published for a control group [1]. In addition, 51% of the participants re-

ported on psychosocial stressors (PHQ-S), 45% had depression symptoms

(PHQ-9) and 36% suered from anxiety symptoms (GAD-7). Unemploy-

ment correlated with PHQ-S (p = 0.029), PHQ-9 (p=0,025) and GAD-7

(p = 0.006). In contrast, employment was a strong predictor for higher

quality of life (p < 0.001). A high fear of disease progression (PAF12, cut-

o 34) was reported by 36% of survivors. e fear of disease progression

correlated with a lower level of education (p = 0.026) and with having

children (p = 0.027). Strain was also caused by psychosocial issues emerge

from daily life topics, e.g. the majority of patients (72%) reported on di-

culties on resumption to work and 62% had problems with sexuality.

Conclusions: Our results clearly indicate that AYA feature a high bur-

den for psychosocial distress aer cancer treatment. In order to improve

quality of life, resumption of work is of utmost importance. erefore,

psycho-oncological and social support needs to become an inherent part

in the aercare of AYA patients.

Reference:

1. Geue et al. Qual Life Res (2014) 23:1377–1386

Disclosure Statement: IH is member of the board of trustees of the German

Foundation for Young Adults with Cancer.

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2018

Radiation

Vorträge

614

Balloon Catheters to extend the Distance between Tumor and

Adjacent Organs at Risk in Interstitial HDR-Brachytherapy of

Liver Malignomas

Peter Hass 1; I.G. Steen 2; Maciej Janusz Powerski 3; Konrad Mohnike 4;

Max Seidensticker 5; Frank Meyer 6; C. Willich 7; Mathias Walke 1;

E. Karagiannis 1; Günther Gademann 1; Thomas Brunner 1; Jens Ricke 5

1Department of Radiation Oncology, University Hospital at Magdeburg,

Magdeburg, Deutschland

2Department of Nuclear Medicine, University Medical Center Charité at Berlin,

Berlin, Deutschland

3Department of Radiology and Nuclear Medicine, University Hospital at

Magdeburg, Magdeburg, Deutschland

4International School of Image-Guided Interventions, Magdeburg, Deutschland

5Department of Clinical Radiology, Ludwig-Maximilian University (LMU) at

Munich, Munich, Deutschland

6Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

7Department of Radiation Therapy and Radiooncology, University Hospital at

Jena, Jena, Deutschland

Purpose: Organs at risk (OAR), which are very close to a clinical target

volume (CTV) can prevent an eective irradiation of the tumor without

a signicant risk of serious side eects. e present study investigated the

extent of the dosimetric eect of distancing CTV from adjacent OAR’s by

means of interventionally applied balloon catheters.

Methods: Consecutive patients with peripheral, predominantly le lobu-

lar hepatic malignancies, which revealed the critical proximity of an OAR

to the CTV in the assessment by gadoxetic acid-enhanced MRI-scans and

the preplanning process, underwent also placement of an interventional

balloon catheter during CT-guided application of interstitial brachythera-

py catheters inserted into the tissue between hepatic capsule and adjacent

OAR. e virtual position of the OAR without balloon catheter was an-

ticipated and contoured in addition to contouring of CTV (which is equal

to Planning Target Volume [PTV] in brachytherapy), liver and further

relevant OAR. e calculated dose values for CTV as well as 1 mL of the

relevant OAR (D1cc) with and without balloon were recorded. e D1cc

of the realized irradiation plan was compared to the D1cc of the virtually

contoured OAR and statistically evaluated.

Results: In 31 cases, one balloon catheter (in 6 cases two) was adminis-

tered without any acute complications. e total duration of the applica-

tion time was increased by 5 min per balloon catheter. Serious late side

eects occurred in one (3%) case only. e median D1cc in the group with

balloon (13.5 Gy) was signicantly lower compared to the virtual OAR

group without a balloon (15.5 Gy) with a corresponding median relative

dierence of -16.3%.

Conclusions: e achievable, signicantly lower dose exposition of the

adjacent OAR reduces the risk of side eects. is may be particularly

important in case of oligo-metastasis since a more ecient irradiation of

the CTV becomes possible consecutively.

Disclosure Statement: Nothing to be disclosed.

Poster

Intensity Modulated Radiotherapy (IMRT) with Carbon

Ion Boost in the Multimodal Treatment of Salivary Duct

Carcinoma

Sebastian Adeberg 1; Paul Windisch 2; Felix Ehret 1; Melissa Baur 1;

Sati Akbaba 1; Thomas Held 1; Denise Bernhardt 1; Matthias Haefner 1;

Jürgen Krauss 3; Steen Kargus 4; Christian Freudlsperger 4; Peter Plinkert 5;

Christa Flechtenmacher 6; Klaus Herfarth 1; Jürgen Peter Debus 1;

Stefan Rieken 1

1Radioonkologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

2Radioonkologie, Zürich, Schweiz

3Medizinische Onkologie, Universitätsklinikum Heidelberg, Heidelberg,

Deutschland

4MKG, Universitätsklinikum Heidelberg

5HNO, Universitätsklinikum Heidelberg, Deutschland

6Pathologisches Institut, Universitätsklinikum Heidelberg

Purpose: To assess outcomes and treatment related toxicity following in-

tensity-modulated radiotherapy (IMRT) and a Carbon Ion Radiotherapy

(CIRT) boost for salivary duct carcinoma (SDC).

Methods: Twenty-eight consecutive patients with SDC who underwent a

postoperative (82%) or denitive (18%) radiation therapy between 2010

and 2017 were assessed in this retrospective single-center analysis. CIRT

boost was delivered with median 18 Gy(RBE) in 6 daily fractions, followed

by an Tomoerapy®-based IMRT (median 54 Gy in 27 daily fractions).

Treatment-related acute toxicity was assessed according to CTCAE Ver-

sion 4.

Results: Tumors were most commonly located in the major salivary

glands (n=25; 89%); 23 patients (82%) received previous surgery (R0:

30%; R1: 57%; R2: 4%; RX: 19%). Median follow-up was 30 months. Four

patients (14%) patients experienced a local relapse and 3 (11%) developed

locoregional recurrence. e two-year local control (LC) and locoregional

control (LRC) was 96% and 93%, respectively. Median disease-free surviv-

al (DFS) was 27 months, metastasis-free survival (MFS) was 69 months,

and overall survival (OS) was 93 months. Acute grade 3 toxicity occurred

in 11 patients (mucositis, dermatitis, xerostomia; n=2 each (7%) were the

most common) and 2 osteonecrosis of the mandibular (grade 3) occurred.

No patients experienced grade ≥4 toxicities.

Conclusions: Multimodal therapy approaches with surgery followed by

IMRT and CIRT boost for SDC leads to good local and locoregional dis-

ease control. However, the frequent occurrence of distant metastases lim-

its the prognosis and requires optimization of adjuvant systemic therapies.

Disclosure Statement: Nothing to declare.

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2018

170

Teaching Radiation Oncology to Medical Students in Germany

– Where do we Stand?

Michael Oertel 1; Matthias Mäurer 2; Daniel Fleischmann 3;

Christian Dietzel 4; David Krug 5

1Universitätsklinikum Münster, Klinik für Strahlentherapie - Radioonkologie,

Münster, Deutschland

2Universitätsklinikum Jena, Klinik für Strahlentherapie und Radioonkologie,

Jena, Deutschland

3Klinikum der LMU München, Klinik und Poliklinik für Strahlentherapie und

Radioonkologie, München, Deutschland

4Universitätsklinikum Halle(Saale), Klinik und Poliklinik für Strahlentherapie,

Halle (Saale), Deutschland

5Universitätsklinikum Schleswig-Holstein – Campus Kiel , Klinik für

Strahlentherapie, Kiel, Deutschland

Purpose: To measure and analyse the teaching situation for radiation on-

cology (RO) in Germany.

Methods: A detailed questionnaire containing multiple-choice and free

text questions covering extent and topics of RO was sent to RO depart-

ments at all university hospitals in Germany and answered by the head of

departments/main lecturers.

Results: 24/35 (68.6%) of RO departments returned completed forms.

Overall, RO plays a role in the curriculum from the 2nd semester onward

with the majority of teaching from the 5th to 10th semester. Most faculties

employ lectures (91.7%), seminars (87.5%) and practical/bedside train-

ing (75.0%), whereas training in radiation biology and medical physics

are less common (25% and 33.3%, respectively). Main topics covered are

general RO (100%), radiation biology (91.7%) and side eects (87.5%).

Concerning dierent organ systems gynaecological (87.5%), urological

(79.2%) and gastroenterological tumors (75%) ranked highest and were

also the predominant subjects for interdisciplinary concepts. Regarding

RO techniques, image-guided and intensity-modulated radiotherapy has

taken centre stage being taught at all faculties, followed by palliative RO

and stereotactic techniques (87.5% each). Notably, all departments oered

a partial rotation (“Wahltertial”) in RO in conjunction with Radiology

and/or Nuclear Medicine departments in the last year of medical school,

while only 70.8% oered a complete rotation in RO. In addition, 57.1%

have taken measures concerning the coming National Competence-based

Learning Objectives Catalogue for medical education.

Conclusions: RO has an integral role in the (clinical) medical education

in Germany, but faces new challenges regarding the development of a

practical, competence-based education, which may require both innova-

tive and interdisciplinary concepts [1,2].

References:

1. Jünger J 2018 Feb;61(2):171–7.

2. Oertel M et al. Strahlenther Onkol. 2019 Jul DOI: 10.1007/s00066-019-01492-z

Disclosures: MO and MM are members of the working group “Medizinstudium”

of the DEGRO.

187

Analyzing Oral Sequelae of Chemo-Radio-Therapy in the

Head-Neck-Region

Benedikt Luka 1; Hatice Bunea 2; Andreas Thomsen 2;

Elsa Beatriz Monroy Ordonez 2; Sibylle Rau 1; Alice Eickenscheidt 3;

Michael Henke 2; Nadine Schlüter 1

1Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-

Universität Freiburg, Deutschland, Department f. Zahn-, Mund- u.

Kieferheilkunde, Klinik für Zahnerhaltungskunde und Parodontologie,

Stiftungsprofessur für Kariesforschung, Freiburg im Breisgau, Deutschland

2Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-

Universität Freiburg, Deutschland, Department für Radiologische Diagnostik

und Therapie, Klinik für Strahlenheilkunde, Freiburg im Breisgau, Deutschland

3Institut für Mikrosystemtechnik – IMTEK, Albert-Ludwigs-Universität, Freiburg

Centre for Interactive Materials and Bioinspired Technologies (FIT) and

Department of Microsystems Engineering, Polymer Synthesis and Surface

Engineering Group, Freiburg im Breisgau, Deutschland

Purpose: Side-eects of chemo-radio-therapy (CRT) of the head-neck-

region can severely impair patients. ere is limited knowledge on

interdependencies of side-eects. A better understanding of underlying

mechanisms, however, may help improving supportive care of these

patients. We intend to study interactions of mucosal, salivary, dental and

cellular parameters of patients with head-neck-cancer during and aer

CRT in an interdisciplinary setting. e study protocol and rst results of

the pilot stage will be presented.

Methods: Patients (n=50) undergoing curative CRT in the head-neck-

region (cisplatinum 2x100mg/m2; 60-70 Gy; 5x2 Gy/week) are examined

one week before, during, at the end, and 8 and 20 weeks aer CRT. A pre-

treatment oral mucosa biopsy is taken for cellular radiosensitivity testing.

On exam1-5 (Ex1-Ex5) mucositis is scored (severity 0-5), saliva collected

(stimulated/unstimulated; ow rate, pH, buering capacity, microbiome,

proteome), dental status assessed (plaque index, pocket depth, bleeding

on probing, caries status (ICDAS)) and quality of life surveyed (xerosto-

mia inventory, quality of life (OHIP-14), food intake frequency, oral hy-

giene). Age/gender matched healthy controls are also included (n=25, no

CRT).

Results: First results (n=11) showed increasing mucositis during CRT

(Ex3: +2.2 points) that almost completely recovered aer CRT. Both, stim-

ulated and unstimulated saliva ow rates were reduced during (Ex3: -71%

and -42%) and stayed constantly low aer CRT (Ex5: -75% and 50%).

Caries-Scores increased constantly during and aer CRT (Ex3: +9.1, Ex5:

+36.9).

Conclusions: CRT impacted most investigated parameters. Our rst re-

sults warrant further evaluations of these factors and their interactions to

ultimately develop strategies aimed to attenuate the grievous side-eects

of CRT in patients with head-neck-cancer.

Disclosure Statement: Funding: University of Freiburg. Previous presentation in

parts: 96th/97th General Session of the IADR 2018/2019, 4. DGZ Tag der Wissen-

scha/Universitäten 2018.

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2018

261

Evaluation of High-Risk Imaging Features for Detection of

Local Progression after Stereotactic Body Radiotherapy

(SBRT) of Malignant Pulmonary Lesions in the Prospective

Stripe -Trial

Sonja Adebahr 1, 2, 3; Katharina Wagner 1; Thomas Brunner 4; Eleni Gkika 1;

Hans-Christian Rischke 1; Juri Ruf 5; Anca-Ligia Grosu 1, 2, 3; Werner Vach 6;

Ursula Nestle 1, 7

1Department of Radiation Oncology, Medical Center, Faculty of Medicine,

University of Freiburg, Freiburg, Germany

2German Cancer Consortium (DKTK) Partner Site Freiburg, Germany

3German Cancer Research Center (DKFZ), Heidelberg, Germany

4Department of Radiotherapy, University of Magdeburg, Magdeburg, Germany

5Department of Nuclear Medicine, Freiburg University Medical Center, Freiburg,

Germany

6Department of Orthopaedics and Traumatology, University Hospital Basel,

Basel, Switzerland

7Department of Radiation Oncology, Kliniken Maria Hilf GmbH

Mönchengladbach, Möchengladbach, Germany

Purpose: Detection of local progression (LP) aer stereotactic body

radiotherapy (SBRT) for lung lesions can be dicult because of radia-

tion-induced lung changes in CT scans. High–risk CT-features (HRF-CT)

for prediction of LP have been proposed, the role of 18F-FDG-PET re-

mains unclear. Here previously dened HRF-CT and 18F-FDG-PET-im-

aging features were evaluated in a prospective SBRT-trial cohort (STRIPE)

under “real-life conditions”.

Methods: Four independent and blinded observers scored follow-up

(FU)-CT and 18F-FDG-PET/CT images of 65 pulmonary lesions aer

SBRT with a structured questionnaire assessing RECIST and HRF-CT

((sequential) enlarging opacity, bulging margin, linear margin disap-

pearance, loss of air bronchogram, craniocaudal growth). If LP was sus-

pected, the respective18F-FDG-PET images were analyzed qualitatively,

then quantitatively. Sensitivity and specicity of HRFs for detecting LP

were calculated using the reference standard dened by clinical long term

courses, including information on imaging and biopsy. Inter-observer

Agreement (IOA) was determined using Cohen’s kappa.

Results: IOA for presence of individual HRF-CT were “slight” (k=0.119

to k=0.288), for overall suspicion on LP aer CT assessment k= 0.308 for

HRF-CT, k= 0.289 for RECIST and k= 0.604 aer qualitative additional

PET assessment. Sensitivity and specicity were 0.22-0.46 and 0.73-0.92

for HRF-CT, 0.30 and 0.94 for RECIST. Additional qualitative 18F-FDG-

PET/CT analysis was highly sensitive (1.0; specicity 0.79), semi-quan-

titative evaluation using SUVmax revealed no further diagnostic benet

(sensitivity 1.0; specicity 0.67). Sensitivity / specicity of CT-assessment

versus qualitative PET-assessment were 0.43 / 0,86 and 1,0 / 0,85, respec-

tively.

Conclusions: While we could neither conrm RECIST nor dened HRF-

CT as reliable predictors of LP, qualitative 18F-FDG-PET/CT assessment

seems to oer more diagnostically accurate information about LP aer

SBRT, not being improved by quantitative 18F-FDG uptake analysis.

263

Immunomodulatory Eects of Photon and Carbon Ion

Irradiation – A Dierentialin Vitro Analysis

Philipp Schröter 1, 2, 3, 4; Laura Hartmann 2; Wolfram Osen 2;

Daniel Baumann 5, 6; Rienk Oringa 5, 6; Stephan Brons 3, 4; Jürgen Debus 1, 3, 4;

Stefan B. Eichmüller 2; Stefan Rieken 1, 3, 4

1Heidelberg University Hospital (UKHD), Department of Radiation Oncology,

Heidelberg, Deutschland

2German Cancer Research Center (DKFZ), Research Group GMP & T Cell Therapy,

Heidelberg, Deutschland

3Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Deutschland

4Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland

5German Cancer Research Center (DKFZ), Molecular Oncology of

Gastrointestinal Tumors, Heidelberg, Deutschland

6Heidelberg University Hospital (UKHD), Department of Surgery, Heidelberg,

Deutschland

Purpose: We compared the immunomodulatory eects of single photon

doses on the murine pancreatic ductal adenocarcinoma (PDA) cell line

PDA30364/OVA to high-LET radiation with carbon (12C) ions in vitro.

Methods: Cells were irradiated by a Gammacell 40 Exactor device (pho-

tons) or through the experimental beam line of the HIT (12C ions). Bio-

logically eective doses (BED) were established through dose dependent

relative biological eectiveness (RBE), determined by clonogenic survival

assay. Cell surface expression of immunomodulatory molecules as well as

cell cycle analyses on PI stained cells were performed by ow cytometry.

Sensitization of target cells for cytotoxic T cell (CTL) mediated lyses was

analyzed via impedance-based cytotoxicity assay.

Results: Dose dependent RBE for 1, 3, 5 and 10 Gy photons were dened

as 10, 7.5, 5 and 3.23, respectively, resulting in equivalent physical doses

of 0.1, 0.4, 1.0 and 3.1 Gy 12C ions. Irradiation induced a dose dependent

G2/M cell cycle arrest and a moderate increase in cell surface expres-

sion of PD-L1, CD73 and MHC class I molecules. CTL mediated lysis of

PDA30364/OVA cells was signicantly increased at higher doses, however

additional checkpoint blockade of PD-L1 did not further enhance target

cell killing signicantly. Eects of 12C ions were generally milder at doses

≤ 5 Gy (BED) reaching an equivalent magnitude at 10 Gy (BED).

Conclusions: Raising single photon doses ≥ 5 Gy, PDA cells were respon-

sive to irradiation with respect to classical radiobiology endpoints and,

moreover, to enhanced CTL mediated target cell killing, thus suggesting

a superiority of hypofractionation over normofractionated regimens. Ir-

radiation with high-LET carbon ions yielded comparable results, however

only at enhanced doses of 10 Gy (BED) with RBE = 3.23. Our data suggest

that the discrepancies among the irradiation eects observed are most

likely caused by the equivalent dose denition via clonogenic survival,

strictly applying a dose dependent RBE.

Disclosure Statement: nothing to disclose.

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672

Carbon-Ion Beam Radiotherapy (C12 RT) as Part of a Trimodal

Therapy for Non-Small Cell Pancoast Tumors: The INKA-Study

Lukas Schaub 1, 2; Henrik Hauswald 1, 2; Hauke Winter 3; Peter Schirmacher 4;

Michael Thomas 5; Uwe Haberkorn 6; Ellerbrock Malte 2; Jürgen Debus 1, 2;

Klaus Herfarth 1, 2

1Department of Radiation Oncology, University Hospital Heidelberg,

Deutschland

2Heidelberg Ion-Beam Therapy Center (HIT), University Hospital Heidelberg

3Department of Surgery, Thoraxklinik, University Hospital Heidelberg,

Deutschland

4Institute of Pathology, University Hospital Heidelberg, Deutschland

5Translational Lung Research Center Heidelberg (TLRC-H), Member of the

German Center for Lung Research (DZL), Thoraxklinik im Universitätsklinikum

Heidelberg

6Department of Nuclear Medicine, University Hospital Heidelberg, Deutschland

Purpose: Pancoast-tumors are rare bronchogenic tumors arising from the

lung apices and inltrating surrounding tissue. A trimodal therapy is gold

standard for locally advanced tumors. is study aims to demonstrate

safety and feasibility of hypofractionated C12 RT within the trimodal

approach.

Methods: INKA is an ongoing prospective, monocentric pilot-study at

the University of Heidelberg. Primary endpoint is safety and feasibility,

characterized by the incidence of grade 3/4 toxicities or treatment inter-

ruptions. Patients are treated with chemotherapy (CHT) according to lo-

cal standard (cisplatin/vincristine). Concomitant with the second cycle,

patients receive C12 RT to the primary tumor and PET-positive lymph

nodes. Median dose is 39 Gy (RBE) in 13 fractions. Surgery is performed

2-3 weeks aer RT. Metabolic response (PERCIST) is assessed by FDG-

PET at inclusion and before surgery. Histopathological remission is

judged according to the Junker classication.

Results: Since 2015, 11 patients were enrolled. 2 drop-outs were regis-

tered at the time of analysis; reasons were subsequent contraindication

for CHT and insucient tolerance of immobilization. None of the treated

patients showed grade ≥3 toxicities. PET-scans performed before surgery

showed partial metabolic remission, i.e. >30% decrease in SUVmax, in

6 patients (67%); 2 patients (22%) showed no change in FDG-uptake; 1

patient (11%) showed complete remission. Histopathological response

was assessed on the resected tissue and showed tumor regression of at

least Junker IIa in all patients. 5 patients (56%) were classied Junker IIb

(<10% vital tumor cells) and 2 patients (22%) showed complete regression

(Junker III).

Conclusions: First results of the ongoing INKA-trial demonstrate that

hypofractionated C12 RT as part of the trimodal therapy is well tolerated

and associated with excellent metabolic and histopathological response

shortly aer neoadjuvant therapy.

Disclosure Statement: Förderung: DFG – KFO214.

686

Intracellular Brachytherapy with 32P-Doped Nanodiamonds

Helmut Bühler 1; Pascaline Nguemgo-Kouam 1;

Bettina Priesch-Grzeszkowiak 1; Anja Grillenberger 1; Mahtab Lashgari 1;

Irenäus A. Adamietz 2

1Institut f. Molekulare Onkologie und Radiobiologie, Marien Hospital, Herne,

Deutschland

2Klinik für Radiotherapie und Radio-Onkologie, Marien Hospital Herne, Herne,

Deutschland

Purpose: Nanodiamonds (NDs) are biocompatible and are therefore suit-

able as carriers for drugs such as cytostatics in cancer therapy. We have

investigated whether they are also suitable as carriers for a radionuclide

that could be used for “intracellular brachytherapy”. erefore the nano-

diamonds were doped with the strong beta-emitter 32P.

Methods: e studies were performed with cultured human breast carci-

noma and glioblastoma cells. As vitality parameters proliferation, motility

and clonogenic survival were determined. e intracellular localization

was analyzed with commercial uorescence-labelled NDs using a uores-

cence microscope.

Results: Investigations with naked NDs showed that no impairment of

the vitality parameters of the cells was observed aer endocytosis. When

32P-NDs with an activity as low as 13 Bq were taken up, proliferation and

especially clonogenic survival were severely reduced, but motility was not

impaired. e eect was signicantly more pronounced in breast cancer

cells than in glioblastoma. e observed intracellular localization of NDs,

which was predominantly perinuclear in breast cancer but more distant

cytosolic in glioblastoma, is consistent with these ndings.

Conclusions: In our model system NDs are not cytotoxic and therefore

suitable for therapy. Doped with a radionuclide, they open up a prom-

ising new option in intracellular brachytherapy. 32P seems particularly

suitable for this purpose due to the high-energy beta radiation and the

short half-life. Targeting to the malignant cells could be achieved via cou-

pled antibodies against specic surface markers of these cells, such as the

HER2 receptor in breast cancer, where a humanized therapeutic antibody

is already available.

Disclosure Statement: Nothing to declare.

697

Outcome and Toxicity after Postoperative Radiotherapy in

Patients with Squamous Cell Carcinoma of the Lip

Kristin Lang

Radioonkologie, Heidelberg, Deutschland

Purpose: Carcinomas of the lips are a relatively common malignancy of

the head and neck region, accounting for roughly one quarter of all oral

cavity cancers. Studies showed ve year survival rates between 85-95%

(1). is study summarizes our institutional experience in utilizing post-

operative RT for patients with squamous cell carcinoma (SCC) of the lips.

Methods: Between 2005 and 2018, 19 patients were postoperative treated

at the University Hospital of Heidelberg for SCC of the upper and lower

lip with a radiotherapy. Median age at diagnosis was 67years (58% male,

42% female). All patients received a median cumulative dose of 66 Gy

(range, 60-70 Gy). Median follow-up was 5.2 years.

Results: e 2-year Kaplan-Meier estimates for OS, PFS, and LDFS were

78.9%, 85.7%, and 100.0%, respectively, and 5-year OS, PFS, and LDFS

rates were 61.4%, 85.7%, and 100.0%, respectively. At the last follow-up,

13 patients (68.4%) were still alive. No patient developed locoregional

relapse; distant relapse was found in two patients (10.5%, distant lymph

nodes and skin metastasis), which occurred in a median of 15 months

aer RT. e analysis showed a signicantly better OS in patients with

higher total RT doses (>60Gy).

Conclusions: Our results demonstrate excellent local control and OS with

acceptable toxicity when utilizing adjuvant radiotherapy in patients with

SCC of the upper and lower lip, despite unfavorable characteristics (T, N,

ECE+).

Reference:

1. Lang K et al., 2018, Intensity Modulated Radiotherapy (IMRT) + Carbon Ion

Boost for Adenoid Cystic Carcinoma of the Minor Salivary Glands in the Oral

Cavity, Cancers

Disclosure Statement: e authors declare no conict of interest.

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738

The Role of Blood Biomarkers in Radiation Therapy for

Thoracic Malignancies

Eleni Gkika 1; Sonja Adebahr 1; Anton Brenner 2; Tanja Schimek-Jasch 1;

Gabriele Niedermann 1; Ursula Nestle 1, 3; Dan G. Duda 4; Anca-Ligia Grosu 1

1University Medical Center Freiburg, Department of Radiation Oncology,

Freiburg im Breisgau, Deutschland

2Ortenau Klinikum Oenburg-Gengenbach, Anästhesie, Deutschland

3Kliniken Maria Hilf GmbH, Department of Radiation Oncology,

Mönchengladbach, Deutschland

4´Massachusetts General Hospital and Harvard Medical School, E. L. Steele

Laboratories for Tumor Biology, Department of Radiation Oncology, Boston,

United States

Purpose: Radiation (RT) of malignant tumors has the potential to induce

immunomodulatory and vascular eects, which can inuence anti-tumor

immunity and normal tissue radiosensitivity. We prospectively evaluated

the role of dierent chemokines and cytokines in patients treated with

radiotherapy for dierent thoracic malignancies concerning survival (OS)

and development of RT induced lung toxicity (RILT).

Methods: Fiy-six patients with lung cancer (n=41), esophageal cancer

(n=14) or thymoma (n=1) treated either with conventionally fractionated

(n=43) or hypo-fractionated (n=13) RT were enrolled prospectively in the

study. Serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6,

IL-8, TNF-α, bFGF, Flt-1, PlGF, VEGF, VEGF-C, VEGF-D were analyzed

by multiplex array (MesoScale Discovery) and measured in a USA CLIA-

certied core at predened time points: before, during and at the end of

RT as well as in the rst and second follow-up. Toxicities were scored

according to common toxicity criteria for adverse events.

Results: We observed upregulation of IL-10, IFN-γ, PlGF, VEGF-D and

downregulation of IL-8, TNF-α, VEGF, VEGF-C during and at the end of

RT. IL-6 was up-, Flt-1 downregulated during RT and down- respective-

ly upregulated at the end of treatment. A higher concentration of IL13,

IL-6 (both p<0.000), IL-1β (p=0.004), IL-8 (p=0.009) and bFGF (p<0.000)

during RT and of IL-6 at the rst follow up (p=0.001) correlated with OS.

Seventeen patients (30%) developed radiologic signs of RILT Grade ≥1

but only two of them (3.6%) developed clinical symptoms (Grade 2). We

could not nd any association between the dierent serial blood biomark-

ers and a higher incidence of RILT.

Conclusions: In our study early changes in blood biomarkers during RT

indicate an early immune response and might play a role in the outcome

of the treatment but don’t seem to contribute signicantly in the develop-

ment of early stage (grade 1) RILT.

739

Stereotactic Body Radiotherapy vs Transarterial

Chemoembolisation in Locally Advanced Hepatocellular

Carcinoma (Heracles: Hepatocellular Carcinoma Stereotactic

Radiotherapy Clinical Ecacy Study)

Eleni Gkika 1; Dominik Bettinger 2; Michael Schultheiss 2; Lars Maruschke 3;

Nico Bartl 1; Simon Kirste 1; Fabian Bamberg 3; Gabriele Ihorst 4;

Robert Thimme 2; Anca-Ligia Grosu 1; Thomas Brunner 1, 5

1University Medical Center Freiburg, Department of Radiation Oncology,

Freiburg im Breisgau, Deutschland

2University Medical Center Freiburg, Department of Internal Medicine, Freiburg

im Breisgau, Deutschland

3University Medical Center Freiburg, Department of Radiology, Freiburg im

Breisgau, Deutschland

4Freiburg University Hospitals, Trial Center - Biometrics, Deutschland

5University Hospitals Magdeburg, Department of Radiation Oncology,

Magdeburg, Deutschland

Purpose: Aim of this prospective trial (HERACLES Study) was to eval-

uate the role SBRT in comparison to TACE in patients with locally ad-

vanced hepatocellular carcinoma (HCC).

Methods: Patients who were discussed in a multidisciplinary tumour

board over a predened period of 12 months were included in the study.

Patients received SBRT when TACE was contraindicated, in case of

progressive disease aer TACE or when TACE was rejected by the patient.

All other patients received TACE. e impact of predened patient and

treatment related factors on QOL (EORTC QLQ-C30 and EORTC QLQ-

CR29) was evaluated. Primary endpoint was feasibility.

Results: Between 06/2016 and 06/2017 19 patients received TACE and 19

patients SBRT, of whom one patient dropped out during SBRT because of

lung progression. In the TACE-arm the median age was 69 years, medi-

an tumor size was 32 mm and median Child-Pugh Score (CPS) 5 points;

two patients were BCLC stage A, fourteen B and two C. Patients in the

SBRT-arm had a median of 73 years, median tumor diameter was 52 mm

and median CPS was 5 points, 9 patients were BCLC stage B and 9 C, 3

of them had a metastatic disease. A portal vein thrombosis was present

in 6 patients only in the SBRT group. Seven patients in the TACE group

received further TACEs and 1 patient a liver transplantation. In the SBRT

group 1 and 2-year overall survival rate was 56% and 74% in the TACE

group (p=0.1). e 1-year local control rate (LCR) was 90% in the SBRT

group and 70% in the TACE group (p=0.2). ere was no statistically sig-

nicant dierence in the QOL at baseline for both groups, and no dier-

ence between baseline and follow-up. One patient had a grade 5 stula in

the SBRT group and one patient had a grade 5 hepatic failure in the TACE

group, 2 a hepatic failure grade 3, 1 grade 3 pancreatitis, 1 grade 3 cholan-

gitis and one abscess in the TACE group.

Conclusions: e primary endpoint feasibility was achieved with 38 pa-

tients included during 12 months in a single center. SBRT leads to good

local control in far advanced HCC with acceptable toxicity compare with

TACE despite of more advanced disease in the SBRT group.

836

Local Radio-Ablation in Hepatic Malignancy – Esprit Study:

A Dosimetric Comparison of Interstitial HDR-Brachytherapy

(IBT) and Body Stereotaxy (SBRT)

Peter Hass 1; Thomas Brunner 1; Mathias Walke 1; Frank Meyer 2; D. Albers 3;

C. Petersen 3; F. Walter 4; Jens Ricke 5; S. Corradini 4

1Dept. of Radiation Therapy, University Hospital at Magdeburg, Magdeburg,

Deutschland

2Dept. of General, Abdominal, Vascular and Transplant Surgery, University

Hospital at Magdeburg, Magdeburg, Deutschland

3Dept. of Radiotherapy and Radiooncology, University Hospital at Hamburg-

Eppendorf, Hamburg, Deutschland

4Dept. of Radiotherapy, Ludwig-Maximilian University at Munich, Munich,

Deutschland

5Dept. of Radiology, Ludwig-Maximilian University at Munich, Munich,

Deutschland

Purpose: To statistically compare relevant dosimetric parameters for

tumor lesion and liver of the both local ablading methods such as:

– interstitial HDR-brachytherapy (iBT) and

– stereotactic body stereotaxy (SBRT)

in the treatment of primary and secundary liver malignomas.

Methods: 1) In this retrospective study (favored by the local ethic

committee), all patients with the characteristics mentioned above (such

as ECOG <2; oligo-metastases; maximum, 6 hepatic metastases) were

enrolled. Aer iBT, the Clinical Target Volumes (CTV = Planning Target

Volume [PTV] in brachytherapy [= iPTV]) were isotropically extended

to stereotactic PTV (sPTV) according to Scheer et al. For these sPTV,

stereotactic plans were calculated, the PTV-surrounding prescription

dosages were according to the iBT plans.

2) e “dose contraints“ for the OAR valid for iBT were strictly taken into

account during SBRT-planning. e following dosimetric parameters of

the iBT- and SBRT-plans were documented for statistical analysis: V5 of

the liver (absolute [cm3] + relative [%]), D99.9 and D90 of the PTV.

Primary end point of the study was the assessment of the dosimetric dif-

ferences between two relevant procedures of radiation therapy.

Results: From 12/2018 to 08/2009, 85 consecutive patients with 1–6 small

and 1 single large oligometastasis (n=61), respectively, or with prima-

ry hepatic tumor lesions (n=24) were enrolled. Median iPTV was 34.66

(range, 0.63–410) cm3, the calculated median sPTV was 73.24 (range,

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6.06–593) cm3, the number of the used iBT-catheters ranged from 1 to 8.

In all four parameters, there were signicant dierences between iBT and

SBRT favoring iBT.

Conclusions: iBT provides signicant advantages from a dosimetric point

of view with regard to a low liver exposure and the eective PTV dosages

D99.9 und D90 (taking into account the OAR – “dose-constraints“). In

additon, the today’s valid ICRU91 norm has not been used for the SBRT-

plan calculation yet. is will be analyzed in a further study.

Disclosure Statement: Nothing to be disclosed.

Rehabilitation and Long-term Burden in Social Medicine (Survivor)

Vorträge

165

Financial and Social Impact of Cancer in Adolescents and

Young Adults (AYA)

Mathias Freund 2; Volker König 1; Gerhard Faber 3; Ulf Seifart 4

1Klinik Bad Oexen, Bad Oeynhausen, Deutschland

2Berlin, Deutsche Stiftung für junge Erwachsene mit Krebs, Berlin, Deutschland

3Celenus Teufelsbad Fachklinik, Abteilung Onkologie, Blankenburg,

Deutschland

4Klinik Sonnenblick, Marburg, Deutschland

Purpose: 16,000 AYA cancer patients from 15 to 39 years are diagnosed

per year in Germany. More than 80% of them can be cured but the disease

and its treatment can lead to serious nancial and social consequences.

Methods: Publications on the nancial situation, employment, and return

to work in AYAs with cancer were analyzed. Data were reviewed and put

into the context of epidemiological and medical data. Furthermore ques-

tions asked in the portal “Young and Cancer” operated by the German

Foundation for Young Adults with Cancer are discussed.

Results: Cancer causes a drastic reduction in the quality of life due to

nancial impairments because employment is reduced or absent. AYA pa-

tients are heterogeneous in diagnosis, social situation and age group. Pub-

lications dierentiate oen poorly due to small numbers and unspecied

selections. Eects of dierent social security systems, legal regulations,

development of economy and labor market are not considered. In Germa-

ny nancial burdens arise in the early course of cancer by out of the pocket

payments and co-payments as well as by gaps in the nancial security in

special groups such as students. Cancer-related fatigue is a major obstacle

for full return to work but does not receive sucient scientic attention.

Long-term survivors experience discrimination trying to become public

ocers or getting housing mortgages and health insurances. Patients’

questions focus on rehabilitation, stepwise reintegration into work, and

disability.

Conclusions: In Germany the data base on social and nancial conse-

quences of cancer in AYA needs to be improved. Dierentiated data

should be obtained by a population-based approach. Data from cancer

registries, social security, and health insurances have to be connected with

data on economic development and working market. Relief from out of

the pocket payments and co-payments is needed. Further steps include

improvements of social security in some groups and steps against discrim-

ination of long-term survivors.

Disclosure Statement: I disclose that I have no conicts of interest.

Poster

113

Learning Personalized Virtual Reality Avatars for

Chemotherapy-Induced Peripheral Neuropathy Rehabilitation

in Breast Cancer

Daria Kurz 1; Cristian Axenie 2

1Akademisches Lehrkrankenhaus der Ludwig-Maximilians Universität München,

Interdisziplinäres Brustzentrum, Helios Klinikum München West, München,

Deutschland

2Technische Hochschule Ingolstadt, Audi Konfuzius-Institut Ingolstadt Lab,

Ingolstadt, Deutschland

Purpose: Virtual Reality (VR) sensorimotor rehabilitation in breast can-

cer survivors is a promising non-opioid alternative to handle Chemother-

apy-Induced Peripheral Neuropathy.

Methods: CIPN has a staggering incidence of up to 60% in taxane-based

therapy, aecting as many as 83% of breast cancer patients [1]. VR reha-

bilitation is still in its infancy [2] but will soon provide digital alter-egos

of patients (avatars) and, using Machine Learning (ML), correct and com-

pensate for painful sensorimotor decits [3]. Our system [4] is a rst at-

tempt at such highly-realistic adaptive VR.

Results: Our experiments show that using ML algorithms for VR avatars

we are able to assess motion patterns and decit levels. We achieve that by

learning underlying correlations in patient’s motion kinematics. We show

that our system oers in average a 35% accuracy improvement in body

joint positions estimation and 83% accuracy improvement in body joint

rotation estimation over state-of-the-art. In such therapies it is assumed

that the delity of virtual to physical world movements is vital for reha-

bilitation, in order to promote the recovery of movement, balance, and

quality of life.

Conclusions: Our system provides a platform for personalized CIPN

VR-based sensorimotor rehabilitation including an ML learnt assessment

of patient motion kinematics to support clinicians to better detect CIPN

symptoms compared to relying solely on patient-reported measures.

References:

1. S. M. Monfort, et al., “Gait, balance, and patient-reported outcomes during

taxane-based chemotherapy in early-stage breast cancer patients,” Breast can-

cer research and treatment, vol. 164, no. 1, 2017.

2. V. C. Tashjian, et al., “Virtual reality for management of pain in hospitalized

patients: Results of a controlled trial,” JMIR Mental Health, vol. 4, no. 1, Mar

2017.

3. M. Schwenk, et al., “Interactive balance training integrating sensor based

visual feedback of movement performance: a pilot study in older adults,” J. of

Neuroeng. and Rehab., vol. 11, no. 1, 2014.

4. VIRTOOAIR: https://gitlab.com/akii-microlab/virtooair

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342

Purdue Pegboard Test – A New Diagnostic Method for the

Assessment of Chemotherapy-Induced Polyneuropathy in

Breast Cancer Patients

Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: Polyneuropathy is a common side eect of neurotoxic chemo-

therapy in breast cancer patients. Aim of this study was the evaluation of

the perdue pegboard test in diagnostics of polyneuropathy induced func-

tional decits.

Methods: 89 patients (mean age 66,4 y) suering on chemotherapy in-

duced polyneuropathy manual dexterity and bimanual coordination were

examined using Purdue pegboard test at the beginning and at the end of a

three-week inpatient rehabilitation.

Results: For the dominant [mean score 12.3 (SD 2.6) to 13.4 (SD 2.5);

eect size d=0.6] and non-dominant side [mean score 12.0 (SD 2.5) to

12.6 (SD 2.7); eect size d=0.4], the functionality during rehabilitation

was signicantly improved (p <0.001). e two-handed test [mean score

9.9 (SD 2.6) to 10.3 (SD 2.3); eect size d=0.2] showed a signicant dif-

ference only (p = 0.05). With the assembly test [mean score 22.7 (SD 7.8)

to 23.5 (SD 8.2); eect size d=0.2], no signicant dierence was found

(p = 0.154) (1).

Conclusions: Purdue pegboard test is a useful diagnostic tool in evalua-

tion and control of functional decits due to polyneuropathy.

Reference:

1. Cohen J. Statistical power analysis for the behavioral sciences Hillsdale. NJ:

Lawrence Earlbaum Associates. 1988;2.

Disclosure Statement: e authors declare that they have no conict of interest.

346

Assessment of Discharge Management in Oncological

Rehabilitation from the Perspective of Patients

Heike Kähnert 1; Harald Fischer 2; Eva-Maria Kalusche-Bontemps 3;

Birgit Leibbrand 4

1Institut für Rehabilitationsforschung, Norderney, Abteilung Bad Salzuen, Bad

Salzuen

2Klinik Rosenberg, Bad Driburg

3MediClin Klinik Reichshof, Reichshof-Eckenhagen

4Salzetalklinik, Bad Salzuen

Purpose: Rehabilitation, with its discharge management, provides ideal

conditions for long-term care for oncology patients. is study aims to

analyze rehab discharge management from the perspective of oncology

patients and to identify measures for a successful rehab discharge man-

agement.

Methods: Data collection was done by questionnaire (oncological inpa-

tients, n=377) at the end and three months aer rehabilitation and by tele-

phone interviews (n = 40) one month post-inpatient. e questionnaires

were analyzed descriptively and the interviews were evaluated by content

analysis.

Results: 48% of oncology patients report at the end of the rehab that there

was insucient guidance about aercare recommendations during rehab

and about 44% rated the aercare as less helpful. Overall, more occupa-

tional aercare recommendations were desired. ree months aer rehab,

54% of the participants gave the discharge management a marking of

“good” or “very good” and 23% the grade “sucient” or worse. Approx-

imately two-thirds of the respondents felt well prepared for life at home.

For about half of the participants, however, the aercare recommenda-

tions were not sucient. Essentials of a successful discharge management

were stated: an individualized aercare, job-related support, information

or contact addresses on ‘rehab-aer-care services’ including scheduling,

cooperation between physicians and rehab-clinics and the developing of

a tele rehab-aercare.

Conclusions: In the future, the rehab-discharge management and es-

pecially the aercare recommendations should be more tailored to the

individual situation of the patient. In addition, tele-aercare should be

organized and strategies developed to promote cooperation between phy-

sicians and rehab-clinics.

Disclosure Statement: Dr. Leibbrand and Dr. Fischer are on the board of VfR e.V.,

Norderney.

350

Reliability of Muscular Strength Assessment with the Pressure

Air Biofeedback (pab®) Device in Prostate Cancer Survivors

Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;

Andries Pienaar 3; Dirk-Henrik Zermann 2; Henry Schulz 1

1Chemnitz University of Technology, Professorship of Sports Medicine / Sports

Biology, Chemnitz, Deutschland

2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster

3University of KwaZulu-Natal, Discipline of Biokinetics, Exercise and Leisure

Sciences, Durban, South Africa

Purpose: Muscular strength is a key component of rehabilitation and

a strong predictor of functional capacity. e pressure air biofeedback

(pab®)devicewas developed to be easily used in a home or clinical testing

environment for diagnosis of muscular strength and allows the measure-

ment of various muscle groups. Aim of the study was to evaluate retest-

reliability of dierent standardstrengthtests in prostate cancer survivors

(PCS) duringuro-oncologicrehabilitation.

Methods: A total of 70 PCS (64±8 yr) performed seven standardized

strength tests (SCP=sit chest press, HGS=handgrip strength, TE=triceps

extension, BC=biceps curl, SHA=standing hip abduction, KE=knee

extensionandHAD=hip adduction) with pab® in a single group 24h-test-

retest design.

Results: Repeated measures ANOVA revealed no systematic error for any

standard strength test with exception of TE test for the le arm (p<0.05).

Relative reliability (ICC 3,1) was ‘excellent’ for HGS and HAD (ICC

range>0.90), ‘good’ for SCP and TE (ICC range 0.75-0.90) and ‘moderate’

for BC, SHA and KE (ICC range 0.64-0.74). e SEM% was lowest for

HGS and HAD (<10%) while the other standard tests ranged between

12-25% with the highest SEM% indicated for BC, SHA and KE (≥20%).

Conclusions: e pab® device demonstrated acceptable test-retest reli-

ability for most of the standard strength tests except the BC, SHA and KE

test. In particular, assessment of handgrip and hip adductor strength was

shown to be highly reliable. With regard to the only moderate reliable BC,

SHA and KE tests, a modication of the testing methodology is necessary

to improve the consistency and to justify its possible application in future

testing protocols.

Disclosure Statement: e authors have no relevant nancial or non-nancial

relationships to disclose.

353

Functional Status and Occurrence of Critical Prognostic Values

in Prostate Cancer Survivors in Uro-Oncological Rehabilitation

Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;

Dirk-Henrik Zermann 2; Henry Schulz 1

1Chemnitz University of Technology, Professorship of Sports Medicine / Sports

Biology, Chemnitz, Deutschland

2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster,

Deutschland

Purpose: Handgrip strength (HGS), 6-minute walk distance (6MWD)

and phase angle (pA) of bioelectrical impedance analysis (BIA) have

been shown to be strong biomarkers of functional status and powerful

predictors of mortality invarious patient groups.eaim of this study

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was to nd out how oen prostate cancer survivors (PCS) demonstrate

HGS, pA and 6MWD below predicted [1] or critical cuto values [2,3]

prior and post a 3-weekuro-oncologicalrehabilitationprogram.

Methods: 125 PCS (66±7 yr) were examined at the beginning (T1) and

the end (T2) oftherehabilitation program. Standardized assessment

included a handgrip strength test following the Southampton protocol

withahydraulic hand dynamometer (Baseline®, HIResTM, Gauge ERTM,

USA), 6-minute-walk-test (6MWT) and BIA (BIA® 3 SF, EgoFit GmbH,

Germany).

Results: At T1,39.2% of PCS presented a critical HGS below individual

cuto which changed to 26.4% at T2. In 20.8%of PCSa critical pA was

detected at T1 with no change of incidence at T2. A 6MWD lower than the

individual predicted value was found in 67.2% of PCA at T1 and in 33.6%

cases at T2. Between T1 and T2 signicant improvements were obtained

for HGS andthe6MWD (HGS:Cohen’s d=0.5; 6MWD: d=1.1; p<0.001)

but not for pA (T1: 5.2±0.8°; T2: 5.2±0.7°).

Conclusions: e data provides knowledge about the occurrence of crit-

ical prognostic values of functional status in PCS in theuro-oncologi-

calrehabilitation setting. Moreover, data has shown that a 3-week reha-

bilitation program is eective in improving strength and endurance but

without aecting the pA. e routine assessment of HGS, 6MWDand pA

may give the option to conduct a risk stratication for PCS which could

aect the ongoing process of survivorship care.

References:

1. Enright & Sherrill: Am J Respir Crit Care Med 1998

2. Steiber: PLoS One 2016

3. Norman et al: Am J Clin Nutr 2010

Disclosure Statement: e authors have no relevant nancial or non-nancial

relationships to disclose.

355

Domain-Specic Consideration of the FACT-P inGerman

Prostate Cancer Survivors before and afterUro-Oncological

Rehabilitation

Alexander Stäuber 1; Marc Heydenreich 2; Gerrit-René Walke 2;

Dirk-Henrik Zermann 2; Henry Schulz 1

1Chemnitz University of Technology, Professorship of Sports Medicine / Sports

Biology, Chemnitz, Deutschland

2Vogtland-Klinik Bad Elster, Department of Urology & Urooncology, Bad Elster,

Deutschland

Purpose: Many of the treatments for prostate cancer adversely aect

health-related quality of life (HRQoL).HRQoL in prostate cancer survi-

vors is measurable bythe internationally most commonly used FACT-P

instrument which comprises the ve domainsof‘physical’, ‘social/family’,

‘emotional‘, ‘functional‘well-being and ‘additional concerns’ (consisting of

items relating specically to prostate cancer and/or its treatment).eaim

of the study was to nd out to what extent a 3-weekuro-oncologicalreha-

bilitationprogramaects the dierent HRQoL domains.

Methods: 128 men (66±7ys) completedtheFACT-P (version 4)prior

and post the rehabilitation program. Dierences were tested for statisti-

cal signicance by Wilcoxonrank sumtest. Eect size (r) was derivedby

dividing the absolute standardized test statistic z by the square root of the

number of pairs. Based on the guideline given by Cohen [1],r = 0.3 was

considered to be a medium and r=0.5 a large eect size.

Results: Statistical analysis revealed signicant improvements with me-

dium eect sizes for all HRQoL domains (p<0.001, r=0.3-0.4) with the

exception of the ‘social/family’ domain (p>0.05). FACT-P total score also

increased signicantly (p<0.001, r=0.5).

Conclusions: Measuring and identifying issues of HRQoL in the pros-

tate cancer survivor may create an opportunity to discuss disease-specic

problems andexchangeinformation transfer from health professional to

patient and vice versa.Uro-oncologicalrehabilitation is very eective in

improving HRQoL and should be oered to all prostate cancer survivors.

References:

1. Cohen: Psychol Bull 1992

Disclosure Statement: e authors have no relevant nancial or non-nancial

relationships to disclose.

356

Body Balance after Cancer Therapy – The Role of Patients Age?

Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: Cancer and cancer therapies (surgery, RT, CT) have a negative

impact on physical and mental well-being. e task of rehabilitation is

overcoming side eects and regaining good quality of life. Physical train-

ing was proven to be very eective (1). e aim of the present prospective

study was to evaluate the eciency of a 3-week rehabilitation program on

the sense of balance in dependence of patient age.

Methods: 89 patients (Ø 62 Jahre) aer cancer therapy were examined. At

the beginning and at the end of a 3-week rehabilitation program a Micros-

wing Balance Test (sense of balance) was performed.

Results: e following results (pre-post-comparison) were obtained.

e stability of the right side in patients under the age of 49 years (n=9)

improved from an average of 67.4% (12.8) to 76.1% (9.2) (p=0.03), be-

tween 50-59 years (n=23) from 62.0% (13.8) to 67.0% (11.6) (p=0.02),

between 60-69 years (n=36) from 54.7% (19.9) to 64.7% (14.2) (p=0.001)

and over the age of 70 years (n=21) from 39.4% (19.7) to 45.0% (20.3)

(p=0.05).

e stability of the le side in patients under the age of 49 years (n=9)

improved from an average of 71.1% (8.4) to 75.9% (6.8) (p=0.02), between

50-59 years (n=23) from 64.4% (16.0) to 69.2% (10.6) (p=0.03), between

60-69 years (n=36) from 55.6% (16.0) to 64.6% (11.8) (p=0.001) and over

the age of 70 years (n=21) from 44.2% (19.1) to 50.4% (18.3) (p=0.005).

Conclusions: A signicant improvement of the sense of balance could be

demonstrated in all age groups. Functional training therapy to promote

endurance, coordination and strength contributes improving physical

function and performance. Patient of all age groups benet form special-

ized oncological rehabilitation.

Reference:

1. Zopf E, Baumann F, Pfeifer K. Körperliche Aktivität und körperliches

Training in der Rehabilitation einer Krebserkrankung. Die Rehabilitation

2014;53(01):2-7.

Disclosure Statement: e authors declare that they have no conict of interest.

357

1H- And 24-Hour Pad Test for Incontinence Diagnostics after

Prostate Cancer Surgery - Assessment of the “Minimal Clinical

Important Dierence” (MCID) and Test-Retest Reliability

Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: e 1- (1hPT) and 24-h Pad Test (24hPT) are used as objective

diagnostic methods for the assessment of postprostatectomy stress uri-

nary incontinence. e aim of this study was to determine the “minimal

clinical important dierence” (MCID) and the test-retest reliability of the

1hPT and 24hPT.

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Methods: 93 patients (mean age 64.0 years) were examined performing a

1hPT and 24hPT at the beginning and at the end of a three-week inpatient

rehabilitation. e Pearson correlation was used for the statistical evalua-

tion of the retest reliability. Values from 0.7 indicate a good repeatability

of the test. e MCID was determined using distribution-based methods

(intra-class coecient (ICC), standard error of the mean (SEM), half stan-

dard deviation (0.5 SD).

Results: e data of all 93 patients could be evaluated. e average urine

loss improved for 1hPT from 22.6g (31.2) to 8.5g (13.2) (p<0.001) and for

24hPT from 242.9g (269.6) to 126.7g (171.1) (p<0.001) before and aer 21

days of rehabilitation. e test-retest reliability resulted in a value of 0.85

for the 1hPT and a value of 0.88 for the 24hPT. e standard error of the

mean was for 1hPT 9.5 and for 24hPT 82.1. e half standard deviation

was for 1hPT 12.6 and for 24hPT 85.7.

Conclusions: e results show that the 1hPT and the 24hPT have a very

good test-retest reliability in everyday clinical practice. e minimum

clinical dierence (MCID) for urine loss reduction that is considered to

be signicant is between 9.5g to 12.6g for the 1hPT and between 82.1g to

85.7g for the 24hPT.

Disclosure Statement: e authors declare that they have no conict of interest.

358

Improvement of Coordination Skills by a Specic

Sensorimotor Training as Part of Oncological Rehabilitation

Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: e combination of classical continence training with oscilla-

tion rod training is an established concept in the rehabilitation of patients

with post-prostatectomy incontinence (1). e aim of this study was to

gure out if the sensorimotor training using an oscillating rod, originally

used for incontinence therapy, also has a positive inuence on the sense

of balance and the reaction time in patients aer radical prostatectomy.

Methods: 47 patients (Ø 64.3 years) aer radical prostatectomy were ex-

amined. All study participants completed a standard therapy program,

consisting of classical continence training, sensorimotor training, endur-

ance training and a moderate strength training. e sense of balance and

the reaction time were measured using Microswing Balance Test (MBT)

and Trac Light Test (TLT) at the beginning and at the end of rehabilita-

tion. e urinary incontinence was evaluated with the 1-h and 24-h test

pad.

Results: e following results (pre-post-comparison) were obtained:

1. highly signicant improvement of postural stability (p<0.001)

• stability right side from 51% to 57%

• stability le side from 53% to 59%

• overall stability from 52% to 58%

2. highly signicant improvement in reaction time, by Ø 12 milliseconds

(p<0.001)

3. signicant improvement of 1-hour pad test (21.2g auf 9.4g (p<0.05))

4. highly signicant improvement of 24-hour pad test (218.1g auf 135.1g

(p<0.001))

Conclusions: A signicant improvement of the sense of balance and the

reaction time was shown. erefore, could be concluded, that not only

the continence apparatus but also the local and deep back and abdominal

muscles as well as the sensory control of the arms, legs and stabilization of

the trunk benet from oscillation rod therapy.

Reference:

1. Heydenreich M, Puta C, Gabriel H, Zermann D, Oscillating pole treatment-a

new eective treatment option for postprostatectomy urinary incontinence.

Oncology Research and Treatment; 2016.

Disclosure Statement: e authors declare that they have no conict of interest.

359

Clinical Eects of Function-Oriented Rehabilitation on Hand

Strength after Cancer Therapy?

Marc Heydenreich; Gerrit-René Walke; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: Improving physical performance is one of the important expec-

tations on uro-oncological rehabilitation. Aim of this study was the eval-

uation of the handgrip strength with a hand dynamometer for diagnostic

during oncological rehabilitation. A comparison with normative reference

values (NRV) was performed.

Methods: 109 patients (mean age 66.8 y) were examined performing

a handgrip strength measurement at the beginning and at the end of a

three-week inpatient rehabilitation. Rehabilitation program included en-

durance, moderate strength and functional training.

Results: e following results (pre-post-comparison) were obtained.

1. signicant improvement of handgrip strength (37.9 kg (8.7) to 40.4 kg

(9.4); p < 0,001)

2. signicant improvement of handgrip strength in patients

• between 40-60 years (n=20) from 41.5 kg (7.9) to 44.7 kg (8.7)

(p = 0.003; NRV=49.7 (2.4))

• between 61-70 years (n=53) from 39.0 kg (8.5) to 41.8 kg (9.1)

(p<0.001; NRV=46.1 (2.7))

• between 71-90 years (n=36) from 34.3 kg (8.3) to 37.6 kg (9.4)

(p<0.001; NRV=39.8 (3.0))

Conclusions: Handgrip strength is a useful diagnostic tool in evaluation

of general health improvements due to oncological rehabilitation. A sig-

nicant increase of handgrip strength was shown however norm values

are not achieved (1). erefore, an appropriate training as learned during

rehabilitation should be continued aer nishing inpatient rehabilitation

as a home training program.

Reference:

1. Steiber N. Strong or weak handgrip? Normative reference values for the

German population across the life course stratied by sex, age, and body

height. PloS one. 2016;11(10):e0163917.

Disclosure Statement: e authors declare that they have no conict of interest.

364

Manual Dysfunction after Breast Cancer Treatment - Inuence

of Specialized Sensorimotor Rehabilitation

Gerrit-René Walke; Marc Heydenreich; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: Around one third of chemotherapy patients develop a neu-

ropathy aer their treatment. Even patients without chemotherapy have

problems in their ne motor skills. e purpose of this study was to nd

out if breast cancer patients with and without chemotherapy benet of a

3-week-rehabilitation program with focus on ne motor skills in occupa-

tional therapy

Methods: 162 patients (Ø 60 years) aer complex breast cancer treatment

were evaluated, 89 patients with chemotherapy and 73 without chemo-

therapy. All patients completed successfully a 3-week-rehabilitation pro-

gram. is included occupational therapy (hand baths, design therapy),

physiotherapy (cell baths, coordinative exercises) and sports therapy (os-

cillation rod therapy). Study diagnostics included a Purdue Pegboard Test

(PPT) for evaluation of manual dysfunctions and the small ber neuropa-

thy screening list (SFNSL) for sensory and pain diagnostics (1, 2).

Results: e following results were obtained:

– All patients achieved following results

• PPT – dominant hand (13.1 to 13.8; p<0.001)

• PPT – non dominant hand (12.5 to 13.2; p<0.001)

• SFNSL (18.6 to 16.3; p<0.001)

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– Patients with chemotherapy

• PPT – dominant hand (12.6 to 13.8; p<0.001)

• PPT – non dominant hand (12.3 to 13.0; p=0.008)

• SFNSL (21.2 to 18.3; p<0.001)

– Patients without chemotherapy

• PPT – dominant hand (13.6 to 13.8; p=0.274)

• PPT – non dominant hand (12.8 to 13.4; p=0.003)

• SFNSL (15.5 to 13.6; p=0.006)

Conclusions: A specialized rehabilitation program aer breast cancer

therapy allows the improvement of manual decits and neuropathic

symptoms. Especially chemotherapy patients with polyneuropathy benet

from occupational therapy.

References:

1. Hoitsma E, De Vries J, Drent M. e small ber neuropathy screening list:

construction and cross-validation in sarcoidosis. Respiratory medicine.

2011;105(1):95-100.

2. Tin J, Asher EJ. e Purdue Pegboard: norms and studies of reliability and

validity. Journal of applied psychology. 1948;32(3):234.

Disclosure Statement: e authors declare that they have no conict of interest.

368

Body Balance, Reaction Time and Handgrip Strength in

Incontinent and Continent Patients after Prostatectomy

Gerrit-René Walke; Marc Heydenreich; Dirk-Henrik Zermann

Private Kliniken Dr. Dr. med. Nebel Vogtland-Klinik Bad Elster GmbH & Co. KG,

Bad Elster, Deutschland

Purpose: Stress urinary incontinence is one of the side eects aer radical

prostatectomy. e identication of inuencing factors for post-prosta-

tectomy urinary incontinence is of great interest. e purpose of this pilot

study was to gure out if the pre-existing body balance and the muscular

situation prior to therapy have an impact on the continence situation aer

surgery.

Methods: 20 incontinent (1h pad test > 50g) and 20 continent (1h pad

test < 1g) patients were examined. Study diagnostics included 1-h-PAD-

Test, Microswing Balance Test (Posturo Kybernetik Test – PKT), a hand

strength dynamometer test and a Sta-drop test (reaction time test).

Results:

1. Incontinent patients have an inferior body balance then continent pa-

tients by trend (39.26% to 44.85%; p=0.349)

2. Incontinent patients have a longer reaction time than continent pa-

tients by trend (18cm to 16.51 p=0.34)

3. Continent patients have a better muscular situation by trend (50kg to

45kg; p=0.06)

Conclusions: e results show that there are dierences between conti-

nent and incontinent patients aer prostatectomy relating to body bal-

ance, muscular strength and reactivity (common health condition) prior

to surgery. Pelvic oor function and trunk stability are inuenced by the

existing body balance of the patients. erefore, a holistic, sensorimotor

(oscillation rod treatment (1)) and functional (continence training) reha-

bilitation program is needed.

Reference:

1. Heydenreich M, Puta C, Gabriel H, Zermann D. Oscillating pole treatment-a

new eective treatment option for postprostatectomy urinary incontinence.

Oncology Research and Treatment; 2016.

Disclosure Statement: e authors declare that they have no conict of interest.

597

Targets for the Prevention of Suicidality in Long-Term

Childhood Cancer Survivors

Mareike Ernst 1; Elmar Brähler 1; Philipp S. Wild 2; Claus Jünger 2; Jörg

Faber 3; Astrid Schneider 4; Manfred E. Beutel 1

1Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik

und Poliklinik für Psychosomatische Medizin und Psychotherapie, Mainz,

Deutschland

2Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Präventive

Kardiologie und Medizinische Prävention, Mainz, Deutschland

3Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum

für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie /

Hämostaseologie, Mainz, Deutschland

4Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Institut

für Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Mainz,

Deutschland

Purpose: Long-term childhood cancer survivors (CCS) are a vulnerable,

understudied population group. ey are at risk for physical and psycho-

social late eects of the disease and its treatment. Previous research has

also attested to elevated rates of suicidal ideation (SI) in CCS, an espe-

cially dangerous indicator of distress. However, there is little knowledge

about potential risk factors which could inform screening and prevention

eorts.

Methods: A register-based sample of 916 adult long-term CCS was

drawn from the oldest German cohort (Mage = 34.58 years [SD = 5.53],

Mage at diagnosis = 6.15 years [SD = 4.28]). Participants underwent medical

assessments and lled out questionnaires. We conducted a linear

regression analysis on current SI, testing predictors of dierent areas:

sociodemographic, social, cancer-related, physical health and health

behavior, and psychological history as well as current distress symptoms.

Results: SI was reported by 73 CCS (8.0%). Besides a CNS tumor diag-

nosis, which was a risk factor, relevant predictors belonged to the social

and psychological domain, comprising previous suicide attempts as well

as current distress (loneliness, anxiety symptoms, depression symptoms,

social phobia symptoms). Living together with a partner was protective.

Conclusions: Decades aer having survived cancer, a subgroup of CCS is

aected by (recurrent) suicidality. CCS’ risk for SI was shaped by individ-

ual medical and psychological history, and by the current social environ-

ment and psychological comorbidities. ere is a need for more screening

eorts, e.g. in primary care settings which take account of these factors.

Interventions reducing CCS’ risk of suicide should target the social do-

main and counteract current stressors.

Disclosure Statement: CVSS is funded by the German Research Foundation

(DFG) (SP 1381/2-1&2, FA 1038/2-1&2,WI 3881/2-1&2). P.S.W. is funded by the

Federal Ministry of Education and Research (BMBF 01EO1503). PSYNA is funded

by the German Cancer Aid (DKH, 70112165 & 70113623). ere is no conict of

interest.

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2018

Sarcoma

Poster

169

Core Needle Biopsy is Superior to Incisional Biopsy for

Dierentiation of Soft Tissue Sarcomas: A Systematic Review

and Meta-Analaysis

Emrullah Birgin 1; Cui Yang 1; Svetlana Hetjens 2; Christoph Reissfelder 1;

Peter Hohenberger 1; Nuh N. Rahbari 1

1Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland

2Universitätsmedizin Mannheim, Abteilung für Medizinische Statistik,

Mannheim, Deutschland

Purpose: Incisional biopsies (IB) has long been considered the gold stan-

dard for diagnosis of so tissue sarcomas (STS) although there is substan-

tial evidence that core needle biopsy (CNB) oers an adequate alternative

technique with less invasiveness and costs. We conducted a meta-analysis

to compare the diagnostic accuracy of both biopsy techniques in STS with

reference to the nal histopathological result.

Methods: A systematic review of literature in the MEDLINE and EM-

BASE databases was performed. Pooled estimates of thediagnosticaccu-

racywere calculated using random eects modeling. Study quality was

assessed by using the QUADAS-2 checklist.

Results: 17 eligible studies (2680 patients with 1582 CNB and 241 IB)

were included. CNB detected correct dignity of lesions with a pooled sen-

sitivity and specicity of 97% (95%CI: 95-98%) and 99% (95%CI: 97-99%)

compared to IB with a pooled sensitivity and specicity of 96% (95%CI:

92-99%) and 100% (95%CI: 94-100%), respectively. Estimated summary

diagnostic accuracy to detect correct STS histotype were as following:

CNB sensitivity 88% (95%CI: 86-90%) and CNB specicity 77% (95%CI:

72-81%) versus IB sensitivity 93% (95%CI: 87-97%) and IB specicity

65% (95%CI: 49-78%). Complications following CNB were signicantly

reduced compared to IB (RR 0.14; 95% CI 0.03 – 0.56; P=<0.01; I2=0%).

e quality of included studies revealed a high risk of bias.

Conclusions: CNB is the superior method to dierentiate STS subtype

with lower complication compared to IB.

Reference:

1. Mehren Mv, Randall RL, Benjamin RS, et al. So Tissue Sarcoma, Version

2.2018, NCCN Clinical Practice Guidelines in Oncology. 2018;16(5):536.

Disclosure Statement: None of the authors have any conicts or nancial support

to disclose.

203

Ewing Sarcoma as Secondary Malignancy in a Heterogeneous

Group of Cancer Patients

Katja Kauertz 1; Heribert Jürgens 2; Michael Paulussen 3; Uta Dirksen 1;

Andreas Ranft 1

1University Hospital Essen, Pediatrics III, Hematology/ Oncology, West German

Cancer Center and German Cancer Research Center, Essen, Deutschland

2University Hospital Muenster, Pediatrics, Hematology/Oncology, Münster,

Deutschland

3Witten/Herdecke University, Children’s Hospital, Pediatrics, Hematology/

Oncology, Datteln, Deutschland

Purpose: Ewing sarcoma (EWS) is the second most frequent bone asso-

ciated tumor in children, adolescents and young adults [1]. Standard of

care is comprised of intensive polychemotherapy, local surgery and radio-

therapy [2]. Among patients with this rare malignancy, secondary EWS

accounts for a small minority of all cases and data regarding EWS as a

secondary malignancy are limited.

Methods: From 1991-2009, two consecutive and nationwide Ewing sarco-

ma trials enrolled 2422 patients. e GPOH database of these two studies

was analyzed for EWS as a secondary malignancy. Kaplan Meier method

was used to estimate event-free survival (EFS) and overall survival (OS).

Results: Among the 2422 patients enrolled in the EICESS 92 and EURO-

EWING 99 studies, 26 cases of secondary EWS were reported. Median

time of follow-up was 3.6 years (range 0.3-14.6) Median age at diagnosis

of secondary EWS was 16.5 years (range 6.7-59.8) compared to 6.4 (range

0.8-53.5) at diagnosis of primary malignancy. Localized Ewing sarcoma

occurred in 15 cases (58%), whereas 11 (42%) patients suered from

metastatic disease. A heterogeneous group of malignancies preceded

secondary EWS; most common primary malignancies included acute

lymphoblastic leukemias (6), lymphomas (5), osteosarcomas (2), and

retinoblastomas (2). ree-year EFS was 0.67 (SE=0.12) for patients with

localized and 0.09 (SE =0.09) for those with metastatic disease. e 3-year

OS was 0.80 (SE=0.10) for patients with localized and 0.18 (SE=0.12) for

patients with metastatic disease.

Conclusions: As a secondary malignancy, EWS accounts for approx-

imately 1% of all reported EWS-cases. e most common hematologic

malignancies within these age groups are consistent with those that pre-

cede secondary EWS. Patient characteristics are comparable to patients

presenting with EWS as a primary malignancy.

References:

1. Grunewald, T.G.P., et al., Ewing sarcoma. Nat Rev Dis Primers, 2018. 4(1): p. 5.

2. Gaspar, N., et al., Ewing Sarcoma: Current Management and Future Approaches

rough Collaboration. J Clin Oncol, 2015. 33(27): p. 3036-46.

307

Impact of Surgical Margins in Patients with Soft Tissue

Sarcomas of the Hand

Mehran Dadras 1; Hans-Ulrich Steinau 1, 2; Ole Goertz 1, 3; Marcus

Lehnhardt 1; Björn Behr 1; Kamran Harati 1

1Klinik für Plastische Chirurgie, Berufsgenossenschaftliches Universitätsklinikum

Bergmannsheil, Bochum, Deutschland

2Sektion Sarkomchirurgie, Klinik für Allgemein-, Viszeral- und

Transplantationschirurgie, Universitätsklinikum Essen, Westdeutsches

Tumorzentrum (WTZ), Essen, Deutschland

3Klinik für Plastische Chirurgie, Martin-Luther-Krankenhaus, Berlin, Deutschland

Purpose: e hand represents a rare but surgically challenging anatomical

location of so tissue sarcomas (STS). Maintaining the surgical aim of

wide resection leads to a high rate of amputations and functional impair-

ment while impact of resection margins on survival in distal extremity

STS remains controversial. We aimed to perform a single institution anal-

ysis of long term results of hand STS to identify prognostic factors.

Methods: All patients operated for localized STS of the hand at our insti-

tution were identied. Uni- and multivariate analysis of factors associated

with 5-year local recurrence free survival (5Y-LRFS), metastases free sur-

vival (5Y-MFS) and disease specic survival (5Y-DSS) were performed.

Results: 51 patients could be identied. Of these 3 received amputations

of single ngers/nger rays while the rest could be treated without any

amputation and marginal resections in the majority of cases and positive

margins in 10% of cases. Aer a median follow-up of 77 months, 5Y-LRFS,

5Y-MFS and 5Y-DSS were 65%, 86% and 91% respectively. Tumor size was

a predictor of all three outcome parameters but positive resection margins

adversely aected LRFS only. Survival outcome was excellent and not in-

ferior to other studies on hand STS with a more radical surgical approach.

Conclusions: Conservative surgical treatment of hand STS with marginal

resection and adjuvant radiation therapy in case of high-grade STS is a

viable treatment strategy leading to a better hand preservation than more

radical surgical approaches at the cost of worse local control but not worse

survival.

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331

Oncologic Impact of Wound Complications in Extremity Soft

Tissue Sarcomas

Mehran Dadras; Pascal Koepp; Christoph Wallner;

Johannes M. Wagner; Alexander Sogorski; Marcus Lehnhardt;

Kamran Harati; Björn Behr

Klinik für Plastische Chirurgie, Berufsgenossenschaftliches Universitätsklinikum

Bergmannsheil, Bochum, Deutschland

Purpose: In various malignancies, complications correlate with dimin-

ished prognosis, however literature on so tissue sarcomas is limited and

inconclusive. e aim of this study was to assess risk factors and the on-

cologic impact of wound complications in primary extremity so-tissue

sarcomas.

Methods: Patients with primary extremity so tissue sarcomas without

dissemination and with clear surgical margins (R0) were analyzed. Groups

with and without wound complications were compared by univariate and

multivariate analysis to identify risk factors. Uni- and multivariate analy-

sis of factors associated with 5-year local recurrence free survival (LRFS),

metastases free survival (MFS) and disease specic survival (DSS) were

performed.

Results: 682 patients were included in the study, wound complications oc-

curred in 94 patients (13.7%) within 90 days. Age, ASA-stage, high tumor

size and grade, tumor location in the foot, neoadjuvant radiation therapy

and operation time represented independent risk factors for wound com-

plications. Patients with wound complications had a signicantly worse

estimated 5-year LRFS of 43.9±6.4% versus 77.1±2.1%. Wound complica-

tions could be identied as a strong independent risk factor for LRFS (HR

3.02[CI 2.03-4.49], p<0.001). 5-year MFS and 5-year DSS were signi-

cantly lower for patients with wound complications in univariate analysis

but wound complications were not signicant in multivariate analysis for

MFS or DSS.

Conclusions: Wound complications aer so tissue sarcomas of the ex-

tremities are associated with worse local oncological outcome. Patients

with high risk of wound complications should be identied and strategies

implemented to reduce surgical complications and possibly improve on-

cologic prognosis.

388

Undierentiated Pleomorphic Sarcomas of the Extremities:

A Single-Institutional Analysis of 179 Patients

Kamran Harati; Ole Goertz; Andreas Pieper; Mehran Dadras;

Björn Behr; Marcus Lehnhardt

BG Universitätsklinikum Bergmannsheil, Plastische Chirurgie, Bochum,

Deutschland

Purpose: Undierentiated pleomorphic sarcoma (UPS) are a frequent

subtype within the heterogenous group of so tissue sarcomas and mostly

occur within the extremities. Surgical resection with negative margins has

been the mainstay of therapy. However, attainment of negative margins in

the extremities can be complicate due to functional important structures.

e aim of this study was to identify prognostic factors in patients with

UPS of the extremities.

Methods: We retrospectively determined the relationship between lo-

cal recurrence-free survival (LRFS), overall survival (OS) and potential

prognostic factors in 179 patients with UPS of the extremities who were

suitable for surgical treatment in curative intent. e median follow-up

time was 4.8 years.

Results: e 5-year local recurrence-free (LRFS) and overall survival

(OS) rate were 58.0% and 73.6%. Negative margin status was associated

with signicantly better LRFS and OS. e rates of LRFS and OS aer 2

years were 75.5% and 87.0% in patients with R0-resected primary tumors

and 60.0% and 75.0% in patients with R1/R2-status (LRFS: P=0.015; OS:

P=0.001). Adjuvant radiotherapy signicantly improved LRFS (5-year:

67.6% vs. 45.7%; P<0.001) and OS (5-year: 82.8 vs. 60.2; P=0.007). Both,

negative margins and adjuvant radiotherapy were found to be indepen-

dent prognostic factors in multivariate analysis.

Conclusions: e data from this study could underscore the benecial

prognostic impact of negative margins on LRFS and OS. However, the

width of negative margins seemed to be not relevant. Notably, adjuvant

radiotherapy was not only able to decrease the risk of local failure but also

improved OS in a signicant manner.

Disclosure Statement: All authors declare that they have no conict of interest.

576

Management of Patients with Gynecological Sarcoma - A

Survey among Gynecologists within the Framework of the

German Registry of Gynecological Sarcoma (REGSA)

Robert Armbrust 1; Philipp Harter 2; Cosima Brucker 3; Hans Georg Strauss 4;

Alexander Mustea 5; Michaela Bossart 6; Mustafa Zelal Muallem 1;

Julia Jordan 7; Jalid Sehouli 1

1Charite University Medicine, Gynaecological Department, Berlin, Deutschland

2Kliniken Essen Mitte, Gynaecological Department, Essen, Deutschland

3Klinikum Nürnberg, Gynaecological Department, Nürnberg, Deutschland

4University Medicine Halle, Gynaecological Department, Halle (Saale),

Deutschland

5University Medicine Bonn, Gynaecological Department, Bonn, Deutschland

6University Medicine Freiburg, Gynaecological Department, Freiburg,

Deutschland

7NOGGO e.V., Studienbüro, Berlin, Deutschland

Trials in Progress:

Prospective Registry of Gynecological Sarcoma:

Management of patients with gynecological sarcoma - a survey among

gynecologists within the framework of the German Registry of Gyne-

cological Sarcoma (REGSA)

Authors: R Armbrust, P Harter, S Brucker, H Strauß, A Mustea, M

Bossart, M Z Muallem, J Jordan, J Sehouli

Purpose: Gynecological sarcoma (GS) are rare neoplasms that make up

1% of all gynecological malignancies. ere is a high clinical and scientic

need to improve the clinical outcome. Specic data of the clinical manage-

ment, including diagnostics, surgery and medical interventions are very

limited.

REGSA is the largest prospective gynecological registry for sarcoma

in Germany. e aim of the register has been to prospectively collect data

of patients with GSs to describe their course of disease, diagnostics and

therapies.

Methods: An electronic case report was designed to register clinical data

from patients with gynecological sarcomas such as disease, surgery, ther-

apy and success of therapy aer informed consent. Additionally, the in-

formation about clinical management as stated by the participating phy-

sicians has also been recorded. is information is completed once per

study site.

e evaluation of the register data is exploratory and descriptive.

ere will be a descriptive analysis of the forms of therapy according to

the dierent types of gynecological sarcoma and their outcome. e REG-

SA study is registered on German Register of Clinical Trials (DRKS) with

the number DRKS00009240.

Results: Patient recruitment started in September 2015 and currently is

still ongoing. Up to date, 125 German study sites together with one Aus-

trian site and one Swiss site have already enrolled 500 patients (status ob-

tained on: 07/2019).

Conclusions: e result of the study might help to initiate multicenter tri-

als and to improve the standard of care. Beside the collection of all medical

data, the experiences and the treatment preferences of the physician are

analyzed by a structured interview.

Disclosure Statement: no conict of interest exists.

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Role of Histone Variants in Sarcoma Pathogenesis

Farina Borken 1; Chen-Jen Hsu 1, 2; Tina Maria Schnöder 1, 2;

Evgeniya Denisova 3;Prya Chudasama 3; Stefan Fröhling 3;

Claudia Scholl 3, 4; Marcus Buschbeck 5; Florian Heidel 1, 2

1Universitätsklinikum Jena, Innere Medizin II, Hämatologie und Onkologie, Jena,

Deutschland

2Leibniz-Institut für Alternsforschung - Fritz-Lipmann- Institut e.V., Jena,

Deutschland

3Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland

4Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

5Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-Germans Trias I

Pujol , Badalona, Spanien

Purpose: Recent studies on tumor cells have suggested that altered epi-

genetic proles including histone variants play a key role in modulating

the functional potential at dierent stages of malignant transformation

(Buschbeck et al. 2017). Multiple variants of the standard histones are en-

coded from a set of ‘orphan genes’ e.g. H2A.Z, H2A.X and macroH2A for

H2 and specically expression of H2A variants has been described in so

tissue sarcoma (STS) (Takahashi et al. 2014). Here we aim to investigate

the role of H2A histone variants in sarcoma pathogenesis.

Methods: Expression of histone variants in 372 human STS samples was

investigated by RNA-sequencing. Functional impact was investigated by

RNAi and validated by CRISPR-Cas9 mediated knockout. Proliferation,

cell cycle and viability of human STS-cell lines were analyzed by ow cy-

tometry and cellular imaging.

Results: When analyzing expression of histone variants in global

transcriptome analyses we found H2AFX, H2AFY and H2AFZ to be

highly expressed in various STS subtypes. To assess for potential functional

dependencies, we genetically inactivated H2AFX, H2AFY and H2AFZ in

a RNAi-based dropout screen in vitro using the human STS-cell line T778.

In this set of experiments especially H2AFX-depleted cells were repeatedly

outcompeted by non-infected cells. ese results could be conrmed by

knockout of H2AFX using the CRISPR-Cas9 system. Interestingly, loss

of competitive advantage was mainly caused by decreased proliferation

(n = 3, p≤0.044*) but did not result in higher rates of apoptosis, eects

that could be recapitulated in other STS cell lines such as MLS-402-91

(n = 3, p≤0.002**) and Fuji (n = 3, p≤0.045*).

Conclusions: In Summary our ndings provide rst evidence for a role

of H2A histone variants in STS biology. Besides dierential expression in

dierent subtypes of sarcoma, specically H2AFX appears to be relevant

for maintenance of cellular competition and proliferation in vitro.

References:

1. Buschbeck M et al. Nat Rev Mol Cell Biol. 2017 May;18(5):299-314

2. Takahashi A et al. PLoS One. 2014 Sep 4;9(9):e106801.

673

A Randomized Phase II Study of Durvalumab and

Tremelimumab Compared to Doxorubicin in Patients with

Advanced or Metastatic Soft Tissue Sarcoma (Medisarc,

AIO-STS-0415)

Viktor Grünwald 1; Philipp Ivanyi 2; Barbara Hermes 3; Armin Tuchscherer 4;

Daniel Pink 5; Sebastian Bauer 1; Lars Lindner 6; Marinela Augustin 7;

Andreas Block 8; Stephan Richter 9; Peter Reichardt 10; Martina Crysandt 11;

Annette Hipper 12; Marc Fischer 12

1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Essen, Deutschland

2Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,

Onkologie und Stammzelltransplantation, Hannover, Deutschland

3Medizinische Universitätsklinik Tübingen, Klinik für Innere Medizin VIII,

Tübingen, Deutschland

4Universität zu Köln, Klinik I für Innere Medizin, Centrum für Integrierte

Onkologie Aachen Bonn Köln Düsseldorf, Köln, Deutschland

5HELIOS Klinikum Bad Saarow, Sarkomzentrum Berlin-Brandenburg, Klinik für

Hämatologie, Onkologie und Palliativmedizin, Bad Saarow, Deutschland

6Klinikum der Universität LMU München, Medizinische Klinik und Poliklinik III,

München, Deutschland

7Universitätsklinik der Paracelsus Medizinischen Privatuniversität Klinikum

Nürnberg, Medizinischen Klinik 5, Hämatologie und Onkologie, Palliativmedizin,

Nürnberg, Deutschland

8Universitätsklinikum Hamburg Eppendorf, Onkologisches Zentrum, II.

Medizinische Klinik und Poliklinik, Hamburg, Deutschland

9Universitätsklinikum Carl Gustav Carus Dresden, University Cancer Center/

Medizinische Klinik I, Dresden, Deutschland

10HELIOS Klinikum Berlin-Buch, Sarkomzentrum Berlin-Brandenburg, Onkologie

und Palliativmedizin, Berlin, Deutschland

11Universitätsklinik RWTH Aachen, Klinik für Hämatologie, Onkologie,

Hämastaseologie und Stammzelltransplantation, Aachen, Deutschland

12AIO-Studien-gGmbH, Berlin, Deutschland

Purpose: So tissue sarcomas (STS) are rare tumors and exhibit sub-

stantial histological diversity. Ecacious targeted 1st line treatment for

advanced/metastatic STS is not available, and the standard therapy has

been anthracycline-based for decades. is strategy shows poor ecacy,

as demonstrated by a median Overall Survival (OS) of 12-20 months.

Several STS subtypes, however, have been shown to express PD-L1, and

immune checkpoint inhibitors (ICI) have demonstrated principle anti-tu-

mor activity in pretreated STS.

Methods: MEDISARC is a multi-center phase II trial that is enrolling

adult treatment-naïve pts with histologically conrmed STS of intermedi-

ate or high grade (FNCLCC) not amenable to surgery with curative intent

and ECOG status 0-2. Chemosensitive histologic STS are eligible. 100 pts

will be randomized 1:1, stratied by ECOG status. Pts in the experimental

arm are treated with xed doses of durvalumab (Q4W) and tremelimum-

ab (Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for

a maximum of 12 months. Doxorubicin treatment in the standard arm is

(Q3W) limited to 6 cycles. OS is the primary endpoint. Secondary end-

points include 2-year OS rate, PFS, ORR, safety, tolerability, and health-re-

lated quality of life (EORTC QLQ-C30). e accompanying translational

research aims to identify prognostic and predictive biomarkers.

Results: 14 centers in Germany are taking part. Enrollment of pts started

in April 2018 and is ongoing.

Conclusions: Our ongoing clinical trial tests the activity and safety of

ICI combination therapy in the 1st line setting. We hypothesize that the

dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab

(CTLA-4) improves overall survival in STS when compared to the stan-

dard of care doxorubicin.

EudraCT No: 2016-004750-15, ClinicalTrials.gov ID: NCT03317457

Reference:

American Society of Clinical Oncology, Inc. Reused with permission. is

abstract was accepted and previously presented at the 2019 ASCO Annual

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782

Impact of Sarcopenia (SMI(+)) In Patients (PTS) with

Advanced or Metastatic Soft Tissue Sarcoma (A/MSTS) during

Multimodal Therapy (MT) as Risk Parameter

Bennet Hensen 1; Dennis Strassmann 2; Viktor Grünwald 3;

Katharina Stange 2; Hendrik Eggers 2; Florian Länger 4; Martin Panzica 5;

Patrick Zardo 6; Hans Christiansen 7; Frank K. Wacker 1; Arnold Ganser 2;

Philipp Ivanyi 2

1Medizinische Hochschule Hannover, Institut für Diagnostische und

Interventionelle Radiologie, Hannover, Deutschland

2MHH, Klinik für Hämatologie, Hämostaseologie, Onkologie und

Stammzelltransplantation, Hannover, Deutschland

3Universitätsklinikum Essen, Essen, Deutschland

4Medizinische Hochschule Hannover, Institut für Pathologie, Hannover,

Deutschland

5Medizinische Hochschule Hannover (MHH), Klinik für Unfallchirurgie,

Hannover, Deutschland

6Medizinische Hochschule Hannover (MHH), Klinik für Herz-, Thorax-,

Transplantations- und Gefäßchirurgie, Hannover, Deutschland

7Medizinische Hochschule Hannover (MHH), Klinik für Strahlentherapie und

Spezielle Onkologie, Hannover, Deutschland

Purpose: Objective parameters in a/mSTS identifying ideal pts for MT are

hardly dened. erefore, impact of sacropenia (SMI+) in MT treated a/

mSTS pts were analyzed retrospectively.

Methods: 89/181 identied pts from 12/98-6/16 with a/mSTS were evalu-

able for analysis (CTs: -14 days before chemotherapy (CTx) onset). Within

perinterventional CTs, lumbar skeletal muscle index (SMI) was measured

with MeVisLab 2.7 by manual segmentation. Optimal tting method de-

ned SMI cut-o (SMI(+) in males (<44) and females (<38). Clinical or

radiological judgment dened progression (cPFS). Descriptive statistics,

Kaplan-Meier-analysis and Cox-regression were administered.

Results: Overall, at onset of CTx 28/89 pts (31%) suered from SMI(+),

and this was associated with overall less aggressive treatments, lower

numbers of medical treatments, less frequently performed surgery, while

radiotherapy was administered more oen. SMI(+) was associated with

less benet from rst line medical treatment compared to SMI(-) (clin-

ical benet rate: 25% vs. 49.2%, p=.032, PFS: 1 (95%-CI: .35-1.65) vs. 2

(95%CI: .67-3.32) months, p=.006). OS was shortened in SMI(+) com-

pared to SMI(-) pts (4 (95%CI:2-6) vs. 16 (95%CI:8.8-23.2) months,

p=.002). SMI(+) tends to be associated with reduced PFS (HR: 1.7 (95%CI:

0.9-2.8), p=.067) and was independently associated with reduced OS (HR:

2.53 (95%CI: 1.5-4.2), p<.001).

Conclusions: a/mSTS pts with sarcopenia tend to receive less aggressive

therapies. A trend of inferior PFS and an independent risk for reduced

OS was identied in SMI(+) pts. However, this analysis is limited due to

its sample size. None the less, SMI(+) might reect an attractive tool for

treatment intensity modulation in a/mSTS patients, avoiding overtreat-

ment in this cohort with dismal prognosis.

Skin Cancer, including Melanoma

Poster

Surgical Treatment of Facial Basal Cell Carcinoma (FBCC). 30

Years of Retrospective and Prospective Studies

Lutz Tischendorf

Praxis MKG Chirurgie, Halle (Saale), Deutschland

Purpose: FBCC are mainly treated surgically. ere are dierences con-

cerning details of the treatment, which is why own studies are summa-

rized as decision-making aid.

Methods: Long-term analyses by means of control of the course of the

disease and reevaluation of the histology. Target criterion: Recurrence

(Kaplan-Meier estimate maximum 25 years).

Retrospective analysis (649 in-patient cases 1948 -1982): Excision with

distance 5 mm. R1- status evaluated only in 1987. Trend to primary defect

closure.

Prospective analysis (832 out-patient cases 1993 – 2007): Excision

with distance 4 mm. Lateral and basal R1-status evaluated in a day. Pri-

mary defect closure.

Analysis of detailed questions (n> 2000)

Results: Controls show excellent oncological and esthetic results.

Recurrence probability for 10 years is determined by R1 and pretreatment

status:

Untreated retrospective cases (n=445) R0: 1.8% R1: 48% (rate R1: 9%)

Untreated prospective cases (n=754) R0: 2% (rate R1: 3%)

Recurrences retrospective cases (n=248) R0 26% R1: 71% (rate R1: 28%)

Recurrences prospective cases (n= 83) R0: 2% (rate R1: 19%)

Detailed questions:

R1 status does not aect survival. Death as result of the tumor is rare

(<0.3%). Secondary tumors occur at a rate of 30% of the patients, with

5% dying. FBCC shortens life expectancy by 5 years compared to normal

population. Unfavorable are locally extended and multicentric FBCCs.

Most FBCCs can be operated on an out-patient basis. Walking disabil-

ities, compliance and blood coagulation disorders can constitute a limita-

tion. Age does not aect prognosis. Complications are rare (4%).

In uncertain basal R1 resections a second-look operation is better than

radiotherapy.

Conclusions: FBCC can be surgically eective treated and oen on an

out-patient basis. Prognostically decisive is the R1-status. Sucient safety

distance as well as lateral and basal marginal cut controls leads to high

oncological safety.

Multiplex Tissue Analysis of the Tumor Microenvironment and

Crucial Factors in Melanoma Pathogenesis

Christian Ostalecki 1; Jung-Hyun Lee 2; Stephan Schierer 1; Lena

Collenburg 1; Gerold Schuler 1; Andreas Baur 1

1Universitätsklinikum Erlangen, Hautklinik, Erlangen, Deutschland

2University of Chicago, Department of Microbiology, Chicago, United States

Purpose: Investigation of the early events of melanocyte transformation

by systematically analyzing human tissue sections by the MELC technol-

ogy.

Methods: e study was made possible by applying the so-called MELC

technology. With this technique, it is possible to visualize up to 100 and

more individual antigens on one tissue section, while preserving the

sub-cellular structure and organization of the sample.

Results: Our analysis reveals that ADAM10 activation is a key step in

the transition from dysplastic nevi to a malignant cell. We detailed this

mechanism and found that a change of the subcellular localization of the

endopeptidase SPPL3 is the crucial event towards malignant transforma-

tion, because this event co-localized ADAM10 with its upstream activator

SPPL3. To get this insight, we systematically analyzed human skin tissue

sections from healthy skin to invasive melanoma. Analyzing the protein

prole in the keratinocyte microenvironment surrounding melanoma

cells was instrumental in our study as it reected the individual steps

of the transformation process. e molecular mechanism we uncover is

plausible as we demonstrate how SPPL3-mediated activation of ADAM10

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is functionally embedded in-between downstream eects of BRAFV600E

and the inactivation of PTEN, two established key players in melanocyte

transformation.

Conclusions: e results of our approach are remarkable not only for the

introduction of novel eectors, but for the involvement of rarely described

factors in the transformation process, including protein levels, their sub-

cellular distribution and the early keratinocyte microenvironment. In

summary, we demonstrate that systematic tissue antigen screening in

combination with molecular analysis provides truly novel insight into

melanoma development.

Prevention of Skin Cancer among Outdoor Workers

Anette Dr. Wahl-Wachendorf

AMD der BG BAU GmbH, Berlin, Deutschland

Purpose: Recognized as an occupational disease are squamous cell carci-

noma and multiple actinic keratosis. Skin cancer is currently the second

most common occupational disease.

Preventive measures have a high impact. In the AMD der BG BAU, we

have conducted precautionary and advisory work on preventive measures

and early detection of skin cancer since 2015.

In Germany, about 3 million outdoor workers are employed, mostly in

the construction industry and agriculture sector.

Experience with preventive measures, such as head protection, sun-

screen and its acceptance, as well as experience with training in training

centers, using modem technologies will be presented.

e AMD der BG BAU consultations and preventive medical

examinations for outdoor workers in the construction industry. In

particular, carcinoma in situ, actinic keratosis and suspicious squamous

cell lesions are identied and subsequent dermatological evaluation are

recommended.

e current concept for the prevention of skin cancer should be put

up for discussion.

Methods: Please copy and paste the corresponding text here.

Results: Please copy and paste the corresponding text here.

Conclusions: Please copy and paste the corresponding text here.

320

Nico: Real World Evidence in Advanced Melanoma; A

National Prospective Non-Interventional Study of Nivolumab

Monotherapy or in Combination with Ipilimumab in Patients

with Advanced Melanoma and in Patients with Adjuvant

Nivolumab Therapy

Dirk Schadendorf 1; Thomas Eigentler 2; Peter Mohr 3; Michael

Weichenthal 4; Daniela Göppner 5; Sebastian Haferkamp 6; Martin Herber 7;

Friedegund Meier 8; Frank Meiß 9; Claudia Pföhler 10; Stefan W. Schneider 11;

Patrick Terheyden 12; Jens Ulrich 13; Jochen Utikal 14; Carsten Weishaupt 15;

Ralf Gutzmer 16

1Department of Dermatology, Venerology and Allergology, University-Hospital

Essen, University of Duisburg-Essen, Essen

2Center for Dermatooncology, Department of Dermatology, Eberhard-Karls-

University of Tuebingen, Tuebingen

3Elbe Clinic Buxtehude, Buxtehude

4Department of Dermatology , University Hospital Schleswig-Holstein, Kiel

5Clinic for Dermatology and Allergology, Justus-Liebig-University, Gießen

6Department of Dermatology, University of Regensburg, Regensburg

7Bristol-Myers-Squibb GmbH & Co. KGaA, München

8Department of Dermatology, Dresden University Hospital and Medical Faculty

Carl Gustav Carus, Technical University of Dresden, Dresden

9Department of Dermatology, Medical Center - Faculty of Medicine, University

of Freiburg, Freiburg

10Department of Dermatology, Saarland University Hospital, Homburg/Saar

11Department of Dermatology and Venerology, University Hospital Hamburg-

Eppendorf, Hamburg

12Department of Dermatology, University of Luebeck, Lübeck

13Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben,

Quedlinburg

14Department of Dermatology, Venereology and Allergology, University Medical

Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim

15Departments of Medicine A - Haematology, Haemostaseology, Oncology, and

Pneumology, University Hospital Muenster, Muenster

16Division of Immunodermatology and Allergy Research, Department of

Dermatology and Allergy, Hannover Medical School, Hannover

Purpose: Nivolumab alone (nivo) and the combination of nivolumab

and ipilimumab (nivo+ipi) for rst and subsequent lines of therapy have

become standard treatment options for advanced melanoma. Most cur-

rently available data are from randomized clinical trials with predened

inclusion/exclusion criteria. erefore, real-world studies are needed to

evaluate the eectiveness and tolerability of nivo and nivo+ipi in a broader

patient population.

Methods: NICO (NCT02990611) is an ongoing, non-interventional study

in Germany associated to ADOREG.

Overall, 950 patients with advanced melanoma, who start therapy with

nivo+ipi or nivo (cohort 1+2, n=750) or with nivo adjuvant therapy (co-

hort 3, n=200) according to marketing authorization in Germany, will be

enrolled. Patients are followed for up to 5 years aer initiation of ther-

apy. e primary objectives are overall survival (OS) in patients receiv-

ing nivo+ipi and relapse-free survival in patients starting nivo adjuvant

therapy. Secondary objectives include OS in patients treated with nivo,

progression free survival, adverse event management and patient-report-

ed outcomes.

Results: Baseline data of 359 nivo+ipi and 205 nivo patients are currently

available, at the next data cut 30.09.2019, interim data of approx. 610 pa-

tients of cohorts 1+2 will describe baseline characteristics and outcome

of patients with a minimum follow-up of 6 months. e data further

provides demographic and disease characteristics of approx. 130 patients

of cohort 3 and comprises safety management of more than 600 treat-

ment-related adverse events documented so far.

Conclusion: We provide the rst eectiveness data of the NICO obser-

vational study in patients treated with nivo or nivo+ipi in routine care

in Germany. Furthermore, information about baseline characteristics in

adjuvant patients and the management of immune related adverse events

in clinical practice is shown. Taken together, these data give valuable in-

sight in the current treatment landscape and outcome in patients with

advanced melanoma.

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Topography-, Age- and Sex-Specic Incidence and Relative

Survival of Cutaneous Squamous Cell Carcinoma in North

Rhine-Westphalia, Germany, 2007-2015

Andreas Stang 1, 2; Ina Wellmann 3; Hiltraud Kajueter 3; Jürgen C. Becker 4;

Adele Green 5; Karl Heinz Jöckel 1; Laura Khil 3

1Institut für Medizinische Informatik, Biometrie und Epidemiologie,

Universitätsklinikum Essen, Essen, Deutschland

2Department of Epidemiology, School of Public Health, Boston University,

Boston, United States

3Krebsregister Nordrhein-Westfalen, Bochum, Deutschland

4Department Translational Skin Cancer Research (TSCR), University Hospital of

Essen, Essen, Deutschland

5QIMR Berghofer Medical Research Institute, Herston, Australien

Purpose: Nonmelanotic skin cancer is frequently not registered by popu-

lation-based cancer registries. e cancer registry of North Rhine-West-

phalia (LKR-NRW) registers these tumors. e aim of this study is to

assess how the incidence and survival of cutaneous squamous cell carci-

noma (SCC) depends on age, sex, and topography.

Methods: With data of the LKR-NRW of the years 2007-2015, we esti-

mated incidence rates (age-specic and age-standardized, European stan-

dard) and age-standardized relative 5-year survival of SCC (genital skin

and remaining skin) by sex and topography.

Results: Overall, 83,650 cases were registered with 8.7% at the skin of the

genitalia (men: 3.0%, women: 16.2%). e SCC incidence of the genital

skin and the remaining skin has increased over time. Age-specic inci-

dence rates of SCC at the genital skin were higher in women than men in

each age group. At the remaining skin, men had higher SCC incidences at

each subsite than women, with the exception of skin of the legs. Age-spe-

cic incidence patterns show two distinct patterns dependent on the lo-

calization. Survival was considerably lower for SCC at the genital skin

(men: 71%, women: 75%) than at the remaining skin (men: 93%, women:

97%). Survival is especially low for SCC at the scrotal skin (67%) and labia

majora (62%).

Conclusions: e increase of the incidence of SCC may be explained by

the introduction of the skin cancer screening program and to some in-

crease in the completeness of registration. When comparing age-specic

incidences between men and women, the age-specic patterns depend on

the localization of the tumors. SCC of the genital skin show a considerably

lower 5-year survival than SCC of the remaining skin.

Disclosure Statement: See extra le.

654

Endocrine Side-Eects inImmune Checkpoint Inhibitor

Combinational (Nivolumab+Ipilimumab) Therapy for

Melanoma Associate with Increased Survival

Caroline Weller 1; Klaus Badenhoop 2; Ümniye Balaban 3;

Roland Kaufmann 1; Markus Meissner 1

1Klinik für Dermatologie, Venerologie und Allergologie, Goethe Universität

Frankfurt, Frankfurt, Deutschland

2Medizinische Klinik 1; Abteilung für Endokrinologie, Goethe Universität

Frankfurt, Frankfurt, Deutschland

3Institut für Biostatistik und mathematische Modellierung , Goethe Universität

Frankfurt, Frankfurt, Deutschland

Purpose: Although previous studies suggest that the endocrine side ef-

fects of immune-checkpoint inhibitor (ICI) combinational therapy with

ipilimumab and nivolumab are underestimated, there is a lack of focused

evaluations and consistent denitions in the clinical setting. e possible

inuence of endocrine side eects on overall survival are up to now not

clearly addressed and should be evaluated in this study.

Methods: In this monocentric retrospective study, patients with ICI com-

binational therapy (Nivolumab + Ipilimumab) in metastatic malignant

melanoma were included. Patients with start of therapy from March 2016

to September 2017 and a follow up period until July 2019 were included.

e incidence, course and therapy of thyroiditis, hyperthyroidism,

hypophysitis including Addisonian crisis and the eects on overall sur-

vival were analyzed.

Results: 44 patients could be included in this study. ere were 27 (61.4%)

dierent endocrine side eects in 22 (50%) patients. Mild to asymptomat-

ic thyroiditis (27.3%) with transient thyrotoxicosis was most frequent aer

a median of 20.5 days (± 11.04) followed by irreversible hypothyroidism

aer a median of 52 days (± 21.12). Hypophysitis was observed in 11.4%

of the treated patients aer a median of 41 days (± 27.58) with resulting

treatment pauses and irreversible adrenocortical insuciency. Endocrine

side eects signicantly correlated with improved overall survival (p =

0.02). e median overall survival was 36 month in the side eect group

versus 7 month in patients without endocrine adverse events.

Conclusions: Endocrine adverse events during ICI combinational thera-

py are more common in the clinical setting than previously thought. Due

to the signicantly improved survival, an increased anti-tumoral activity

can be assumed when endocrine side eects occur.

Disclosure Statement: CW, KB, RK: no conict of interest; MM: Advisory and

speaker function for BMS, MSD, Merck.

709

With Three-Dimensional Histology, the Area of the Studied

Resection Margins of Excidates is up to 5,000 Times Higher

than with Conventional Histology

Irina Belova

Charité - Universitätsmedizin Berlin, Chirurgische Klinik (CVK), Berlin,

Deutschland

Purpose: In a conventional histology (CH) using parallel cuts, the areas

between the slices remain unrepresented in the histological slides, which

can lead to incomplete removal of the tumor along the resection margin

(RM) and worsen the treatment results. For guaranteed detection of tu-

mor inltrates in the RM, the excidate should be prepared by 3D histology

(3D H): separating the thin vertical lateral margin strip (marginal section

(S)), then horizontal – a thin layer of the lower side (basic S) and nally – a

cross section of the remaining middle part (middle S). Marginal and basic

S are to be examined for the presence of tumor inltrates, and the mor-

phological type of the tumor is determined by the middle S. We compared

the eciency of 3D H and CH in skin cancer using a mathematical model.

Methods: 18 variants of sizes of excidates in the form of a circular cylin-

der were examined: 1, 2, 3, 5, 7, 10 cm in diameter and 0.5, 1 and 1.5 cm

in height. It was assumed that for CH, excidates are prepared as follows:

with a diameter ≤ 2 cm – in parallel S completely, starting from the center

(middle S), and from it – to the margins of the excidate, and with a diam-

eter > 2 cm, three S were made in the center and one on each sides of the

excidate. e thickness of the S both in CH and in 3D H was taken to be

2 mm. Aer paranization, histological ne slices, 5 microns thick, were

made and examined under a microscope: in the CH – from the center of

each S, and in 3D H – from the outer margin of the S. e percentages of

the studied area of RM in 3D H and CH were calculated and compared,

the percentage of the area of useful examination (to determine the tumor

type and to detect tumor inltrates along the RM) in the total studied area

was determined.

Results: CH provides a check of the RM by only 0.02-0.2%, and 3D H – by

85-100%. In CH with 5 S – 70-75%, and with 9 S – 87% of working time

and expendable material is wasted.

Conclusions: CH does not guarantee the detection of tumor inltrates

in the RM and does not protect the patient from recurrence aer surgical

removal of the tumor. It is more reasonable to use 3D H for the evaluation

of the excidate with skin cancer.

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816

Treatment Reality of Patients with BRAF-Mutant Advanced/

Metastatic Melanoma in Germany, Austria and Switzerland in

the Era of Choice

Sebastian Haferkamp 1; Ingrid Wolf 2; Mareike Alter 3; Dirk Debus 4;

Bastian Schilling 5; Robert Hunger 6; Patrick Terheyden 7;

Camille Lea Gerard 8; Deborah Zihler 9; Andreas Pinter 10; Jochen Utikal 11;

M. Sachse 12; Thomas Haalck 13; Ralph Zachariah 14; Johanna Mangana 15

1Klinik und Poliklinik für Dermatologie, Universitaetsklinikum Regensburg,

Regensburg, Deutschland

2Dermatologie und Venerologie, Universitaetsklinikum Graz, Graz, Österreich

3Klinik für Dermatologie und Venerologie, Universitätsklinikum Magdeburg,

Magdeburg, Deutschland

4Hauttumorzentrum Nürnberg, Paracelsus Universität, Nürnberg, Deutschland

5Hautklinik, Universitätsklinikum Würzburg, Würzburg, Deutschland

6Abteilung Dermatologie, Universitätsspital Bern, Bern, Schweiz

7Hautklinik, Universitaetsklinikum Schleswig-Holstein

8Oncology Department, Université de Lausanne, Lausanne, Schweiz

9Abteilung für Onkologie, Hämatologie und Transfusionsmedizin, Kantonsspital

Aarau AG , Aarau, Schweiz

10Klinik für Dermatologie Venerologie und Allergologie, Universitätsklinikum

Frankfurt, Frankfurt, Deutschland

11Deutsches Krebsforschungszentrum (DKFZ) , Universität Heidelberg,

Heidelberg, Deutschland

12Klinik für Dermatologie, Allergologie und Phlebologie, Klinikum Bremerhaven

Reinkenheide gGmbH, Bremerhaven, Deutschland

13Ambulanzzentrum des UKE GmbH, Universitätsklinikum Hamburg-Eppendorf,

Hamburg, Deutschland

14Medizinische Onkologie und Hämatologie, Kantonsspital Winterthur,

Winterthur, Schweiz

15Dermatologische Klinik, Universitätsspital Zürich, Zürich, Schweiz

Purpose: Due to the rapid development of the treatment landscape,

multiple options are available for the treatment of patients (pts) with

BRAF-mutant advanced/metastatic melanoma. Targeted therapies (TT)

of BRAF and MEK inhibitor combinations or checkpoint inhibitors (IO)

in monotherapy or in combination are used. e present analysis shows

the current treatment choices and their reasons in daily routine treatment

in Germany, Austria and Switzerland.

Methods: Retrospective and anonymous documentation of the rst- to

third-line treatments outside of clinical trials (treatment start between

January 2016 and September 2018) in pts with advanced/metastatic

BRAFV600E/K-mutant melanoma and the reasons for treatment choice.

Results: Data of 140 pts treated with 242 treatment lines at 15 clinics were

analyzed (52% male; median age 59 years, ECOG PS 0 or 1: 75.7%; ele-

vated LDH: 34.3%; stage IV M1c: 25.0%; M1d: 22.1%). 74 pts entered the

second and 28 pts the third line treatment. e choice between TT and IO

was well-balanced (1st: TT 50.7%; IO 49.3%; 2nd: TT 50.0%; IO: 45.9%).

In general, the treatment type was switched between the treatment lines.

e main reason for choosing a treatment type were remission pressure

for TT and physician’s preference for IO. For TT, dabrafenib + trametinib

was predominantly administered (70.0%); vemurafenib + cobimetinib

was used in 26.0% of the pts. For IO, more pts received monotherapy reg-

imens (56.3%) than combination treatment (43.8%). e main reasons for

choosing specic drugs were their toxicity proles (TT) and physician’s

preference (IO). Main reasons for treatment discontinuation were pro-

gression (TT 45%; IO 45%) and toxicities (TT 15.0%, mostly dermatolog-

ical; IO 17.9%, mostly gastrointestinal (nearly all in IO combinations)).

Conclusions: In the treatment of patients with BRAF-mutant advanced/

metastatic melanoma, modern substances were used with an equal distri-

bution between TT and IO. e reasons for choosing between TT and IO,

or substances within the groups, were dierent.

Disclosure Statement: Financing by Pierre Fabre Pharma.

823

Single Center Experience: Use of Talimogene Laherparepvec

(TVEC) in the Elderly: A (COST)-Eective Therapy-Option with

Low Side-Eects ?

Johannes Kleemann; Manuel Jäger; E. Valesky; Roland Kaufmann;

Markus Meissner

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum

Frankfurt, Frankfurt am Main, Deutschland

Purpose: Talimogene laherprapevec (T-VEC), a genetically modied her-

pes simplex virus (HSV-1), has been approved for the intralesional ther-

apy of locally advanced malignant melanoma (AJCC IIIB- IVM1a) since

2016 in Germany. In the randomized controlled Phase III trial (OPTiM),

T-VEC achieved in the above cohort a response rate (ORR) of 46.0% and

a durable response rate of 28.8%. Adverse event grade 3 or higher were

rare. To date, little data is available on the use of T-VEC outside of clinical

trials, particularly with regard to the treatment needs of elderly patients.

Methods: In the present retrospective evaluation we examined the data of

11 elderly patients(minimum age of 65 years at the start of treatment) suf-

fering from malignant melanoma , who were treated with T-VEC outside

of clinical trials at the University Hospital Frankfurt from August 2016

to May 2019. erapy response was measured by overall response rate

(ORR) and sustained tumor response rate (DRR). Patient specic data,

side eects and therapy costs were collected and evaluated.

Results: 82% (n=9) of the patients were in AJCC stage III at the start of

therapy, 18% (n=2) in IVM1a. e median age was 83 years. 18% (n=2)

of the patients under therapy with T-VEC achieved a complete response,

55% (n=6) had a partial remission, 9% (n=1) achieved a stable disease and

18% (n=2) showed progressive disease. us, the tumor control rate was

82% (n=9). Treatment related irreversible and serious side eects (≥ grade

3) were not observed. One patient died of a non-associated myocardial

infarction during the observation period. e mean therapy costs in the

investigated population were in the same range as the minimum annual

therapy costs of T-VEC according to pharmacy retail prices.

Conclusions: In this special cohort of elderly patients, the high tumor

control rate of 82% shows a good ecacy of T-VEC in the therapy of ma-

lignant melanoma under real-life conditions. With the regard to the short

average duration of treatment and the low side eect rate, T-VEC oers a

good therapy alternative for aged patients

856

Validation of the 8th Edition TNM Classication For Stage III

Melanoma Patients in a Single German Referral Center

Nina Stöckle 1; Axel Hauschild 1; Katharina Kähler 1; Michael Weichental 1

1Universität Kiel, Klinik für Dermatologie, Kiel, Deutschland

Purpose: In the 8th edition of the AJCC and UICC TNM classica-

tion rules for melanoma with locoregional spread (stage III) have been

changed substantially. As a result, the estimated 5-year survival rates for

e.g. stage IIIA have improved dramatically, making stage IIIA more favor-

able than stage IIB and IIC. Concerns have been raised as to the validity of

the underlying outcome database, still some retrospective re-evaluations

suer from potential selection bias during follow-up.

Methods: We attempted to evaluate 5-year survival follow-up for stage

III melanoma patients diagnosed between with a loss-to-follow-up rate

below 10% and with a primary focus on prospectively followed primary

diagnoses. We evaluated releapse-free survival (RFS) and overall survival

(OS) and calculated 5-year rates using Kaplan-Meier product limit

estimates.

Results: We present follow-up data on 277 patients with 7th edition stage

III melanoma primarily diagnosed between January 1 2003 and Decem-

ber 31 2013. e estimated melanoma specic 5-year survival rates were

87.8%, 78.7%, 57.4%, and 25.0% in stages IIIA (n=49), IIIB (n=74), IIIC

(n=143), and IIID (n=8), respectively.

Conclusions: e usability of the new TNM classication for stage III

melanoma could be conrmed. Survival rates where higher as compared

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2018

to the corresponding 7th edition rates, but somewhat lower as published by

the AJCC melanoma international database.

Reference:

1. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-ba-

sed changes in the American Joint Committee on Cancer eighth edition cancer

staging manual. CA Cancer J Clin 2017;67:472-92. on cancer eighth edition

cancer staging manual. CA. Cancer J. Clin. 2017;67:472-492

Disclosure Statement: none to disclose.

Supportive Care

Vorträge

743

Institutional Strategies for Addressing Complementary or

Alternative Medicine (CAM). A Qualitative Study with Health

Professionals in (Pediatric) Oncology

Ulrike Handke 1; Pia Klatt 2; Jan Schildmann 3; Christin Kohrs 2;

Barbara Stein 2; Markus Horneber 1; Daniela Reis 4; Alfred Längler 4

1Universitätsklinik für Innere Medizin 5 – Schwerpunkt Onkologie/Hämatologie,

Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Nürnberg,

Deutschland

2Universitätsklinik für Psychosomatische Medizin und Psychotherapie,

Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Nürnberg,

Deutschland

3Institut für Geschichte und Ethik der Medizin , Martin-Luther-Universität Halle-

Wittenberg, Halle (Saale), Deutschland

4Universität Witten/Herdecke, Fakultät für Gesundheit, Professur für integrative

Kinder- und Jugendmedizin, Gemeinschaftskrankenhaus Herdecke, Abteilung

für Kinder- und Jugendmedizin, Herdecke, Deutschland

Purpose: is paper explores attitudes and experiences of health profes-

sionals in (pediatric) cancer care whether - and if so, how CAM consulta-

tion and/or treatment should be integrated into clinical care.

Methods: Qualitative semi-structured in-depth interviews with experts

in (pediatric) oncology in Germany. Sampling started from a convenience

sample with subsequent elements of snowball sampling. All interviews

were audiotaped and transcribed ad verbatim. Qualitative analysis of

data was conducted according to principles of content analysis by two re-

searchers independently.

Results: Interviews were conducted with 15 pediatric oncologists, 13

physicians with clinical experience in the care of adult cancer patients,

2 nurses, 2 psychologists and 1 dietician. Interviewees understanding

of CAM varied considerably. ere was agreement among interviewees

regarding a perceived need for institutional services on information and

possible CAM treatment oers. Reported examples of individual activities

to inform about or provide CAM measures were usually initiated by sin-

gle professionals with strong interest in CAM but not embedded into an

overall institutional strategy. Lack of evidence was not a general reason for

refusal, in fact integrating CAM measures was viewed by some as a chance

to create an evidence-base. Structural challenges encompassed nancial

resources, time and rooms allocated to the provision of such services. e

acceptance by health professionals was quoted as another relevant factor

furthering or hindering the institutional implementation of CAM (infor-

mation) services in cancer care.

Conclusions: e interviewed experts in principle agree on the need

for establishing CAM related services on an institutional level. However,

there were dierences regarding their understanding of CAM and the ele-

ments of CAM related services.

Disclosure Statement: is work is part of the collaborative research project

“Kompetenznetz Komplementärmedizin in der Onkologie – KOKON”, funded by

Stiung Deutsche Krebshilfe, Bonn, Germany (Project No. 70112458)

Poster

Feasibility of Yoga Intervention in Curative and Palliative

Cancer Patients with Fatigue

Teresa Zetzl; Agnes Renner

Interdisziplinäres Zentrum Palliativmedizin, Universitätsklinikum Würzburg,

Würzburg, Deutschland

Purpose: Yoga interventions achieve growing attention in cancer care to

reduce side eects of the treatment 1. e purpose of this pilot study was

to test the feasibility of an 8-week yoga-therapy for palliative and curative

oncological patients who suer strongly from fatigue. We want to inves-

tigate the eectiveness and any necessary changes to the program or re-

cruitment.

Methods: e eligible participants (fatigue intensity ≥4, impairment ≥ 5)2

were randomly assigned to either the intervention group (IG) or the con-

trol group (CG). e IG received 8 units of yoga, one hour per week. At

the beginning and aer 9 weeks, fatigue, quality of life (QoL) and depres-

sion were assessed by questionnaire.

Results: Within a recruitment period of 5 months, 25 out of 241 eligi-

ble patients were enrolled for the study (participation rate=10.3%). e

participants (12 IG, 13 CG), mean age 61.8 years (STD 13.15), were 76%

women, 20% under palliative treatment and predominantly aected by

breast cancer (56%). 66% of participants in IG attended more than 50%

of yoga classes. 6 participants (3 IG/3 CG) discontinued the study due

to overlapping appointments (33%), poor general condition (33%) or no

reasons given (33%). e satisfaction regarding yoga class (5.9/6), selec-

tion of yoga poses (5.6/6) and instruction by the yoga therapists (5.8/6)

was very high.

In an explorative peer-protocol analysis with participants who attend-

ed more than 50% of the yoga classes signicant dierences in depres-

sion score (time x group interaction) were reported (p=.007, d=1.63). No

signicant interactions were found in physical, emotional and cognitive

fatigue and QoL.

Conclusions: ese initial results suggest that yoga is well accepted and

should be further explored with a larger sample size. Due to the low par-

ticipation rate the inclusion and exclusion criteria must be discussed. Fur-

ther research should be done into the reasons for non-participation in

order to reduce it.

References:

1. Buart et al., 2012

2. Fischer, 2013

Disclosure Statement: TZ and AR report grants from Deutsche Krebshilfe, during

conduct of study

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124

Prio-Practical and Patient-Oriented Recipe Development for

Oncology Patients

Barbara Scheerer 1; Daniel Buchholz 2; Heike Sanchez 3; Jana Schmunz 4;

Walburga Träger 5; Lars Selig 6; Volker Heinemann 1; Nicole Erickson 1

1 Ludwig Maximilian‘s University, Krebszentrum – CCC MünchenLMU –

Comprehensive Cancer Center, München, Deutschland

2Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Staatlich

anerkannte Schule für Diätassisten

3Universtitätsklinikum Ulm, Akademie für Gesundheitsberufe | Schule für

Diätassistenz, Ulm-Wiblingen, Deutschland

4Charité Gesundheitsakademie , Ausbildungsbereich Diätassistenz, Berlin,

Deutschland

5St. Franziskus – Schule für Gesundheitsberufe , Schule für Diätassistenten,

Münster, Deutschland

6Universitätsklinikum Leipzig, Ernährungsteam/Ernährungsambulanz, Leipzig

Purpose: While nutrition recommendations play an integral role in the

maintenance of nutrition status, it is important to dene barriers und fa-

cilitators to the implementation of nutrition recommendations and pro-

vide practical patient-oriented, scientically based solutions.

Methods: In this mixed methods study, the Patient Generated Subjective

Global Assessment provided validated quantitative information pertain-

ing to nutrition-related symptom burden (NRSB), and nutrition status.

Qualitative methods provided criteria for development of recipes targeted

at NRSB and the nal questionnaire assessing barriers und facilitators to

the implementation of nutrition recommendations, which will be ana-

lyzed quantitatively via SPSS v.25.

Results: Following the criteria elicited from structured interviews with

patients (n=8) and professionals (n=10), 52 recipes aimed at easing the

NRSB were developed, and pre-tested for taste, texture, appearance, and

ease of preparation in the test kitchens by dietitians and dietetic students

spread over 7 locations in Germany. Selected recipes are further being

quantitatively assessed for acceptance and utility. Recruitment is ongoing

(so far n=45) for the questionnaires which will be analyzed quantitatively

in Autumn 2019.

Conclusions: is study will contribute to a more practicable, patient-

oriented approach to managing the NRSB and provide suggestions for

tailoring information aimed at malnutrition prevention. Results along

with exemplary recipes will be presented at the Congress. Free access to

the recipes via internet will be provided.

References:

1. Beehler et al. Mil Med. 179, 9:998, 2014.

2. Conradie et al. S Afr J Clin Nutr 2009;22(4):177-184

Disclosure Statement: DKG provided nancial support.

134

Education about Complementary Medicine: Evaluation of a

Concept for Leaders of Cancer Self-Help Groups

Martina Jablotschkin 1; Hans Helge Bartsch 2; Markus Horneber 3;

Joachim Weis 1

1Comprehensive Cancer Center - Department of Cancer Self-help Research,

University Clinic Center Freiburg, Freiburg, Deutschland

2University Clinic Center Freiburg, UKF Reha gGmbH - Department of

Oncological Rehabilitation, Medical Center, Freiburg, Deutschland

3Paracelsus Medical University, Klinikum Nuernberg, Department of Internal

Medicine - Divisions of Oncology/Hematology and Pneumology, Nürnberg,

Deutschland

Purpose: Many cancer patients have a need for information about com-

plementary and alternative medicine (CAM). e purpose of the study

(KOKON subproject P7, funded by German Cancer Aid) [1] was to im-

plement and evaluate a CAM educational concept for group leaders of

cancer self-help groups, which was developed in a pilot study in cooper-

ation with health professionals and representatives of cancer patients ad-

vocacy organizations. Its aim was to promote an open exchange of expe-

riences with CAM, to impart reliable information sources and to sensitize

for untrustworthy CAM oers.

Methods: Self-help group leaders were trained in Germany to carry out a

CAM training in their groups. e trainings were evaluated in terms of ac-

ceptance and feasibility by group leaders and members. A follow-up ques-

tionnaire for the group members six months aer the training to prove its

sustainability and potentially changed information seeking behaviors or

attitudes towards CAM will be analyzed at the end of 2019 (T2).

Results: N=49 of N=577 trained group leaders implemented the training

in their groups and felt condent to moderate it using provided mate-

rial. e trained group members (N=419) were satised with selection

and comprehensibility of contents, appreciated the possibility to exchange

CAM experiences and agreed that the training imparts reliable informa-

tion sources, 91% would recommend it.

Conclusions: e preliminary results indicate that this innovative educa-

tional concept could be a good option to inform cancer survivors about

CAM in addition to consultation by experts.

Reference:

1. Witt, C.M., Bartsch, H.H., Güthlin, C. et al. (2017). Kompetenznetz Komple-

mentärmedizin in der Onkologie (KOKON). Ein wissenschalicher Beitrag

zur Verbesserung der Versorgung. Forum 2017. https://doi.org/10.1007/

s12312-017-0311-1

Disclosure Statement: e authors declare that there are no conicts of interest in

terms of the contents of this publication.

157

Whole Body Vibration Exercise Aects Bone Metabolism and

Improves Physical Performance in Patients with Monoclonal

Gammpathy of Undetermined Signicance

Lothar Seefried 1; Bernhard Engelmann 2; Franca Genest 1;

Johanna Strömsdörfer 2; Constantin Lapa 3; Freerk Baumann 4;

Billy Sperlich 5; Franziska Jundt 2

1Orthopädische Klinik König-Ludwig-Haus, Würzburg

2Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,

Deutschland

3Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg,

Deutschland

4Innere Medizin I, Uniklinik Köln, Deutschland

5Institut für Sportwissenschaft, Universität Würzburg

Purpose: Monoclonal gammopathy of undetermined signicance

(MGUS) is a pre-malignant condition in which abnormal monoclonal

proteins are produced by plasma cells in the bone marrow. Patients with

MGUS have an increased risk for bone fractures potentially due to in-

creased cortical porosity.1 In our clinical pilot study we evaluated the im-

pact of whole body vibration (WBV) exercise on bone turnover, structure

and physical functioning.

Methods: Fieen MGUS patients (62.5 ± 7.8 yr; n=9 female) performed

WBV two times per week for 30 minutes over twelve weeks. Ten patients

continued WBV training for additional twelve weeks. Primary endpoints

were changes in bone density parameters (quantitative computer tomog-

raphy) and bone turnover markers. Measures of functional and activity

testing served as secondary endpoints.

Results: In females (n=9) we observed a signicant increase in bone

structural parameters such as cortical thickness (P=0.016) at the tibia over

24 weeks. In the entire cohort a signicant decrease in the bone biomark-

ers Dickkopf1/DKK1 (P=0.012), Alkaline Phosphatase (P=0.006), was

accompanied by an increase in Sclerostin levels (P=0.015). Highly signif-

icant improvements in physical functioning were measured by the Chair

Rise Test (P=0.001), Timed up and go (P=0.001) and 6-minute Walk Test

(P=0.001) aer 24 weeks. No exercise-related adverse events or skeletal

fractures were observed during the study.

Conclusions: Our study demonstrates that WBV improves bone turnover

parameters and physical functioning, particularly in females with MGUS.

Future studies are needed to show whether WBV has an impact on frac-

ture risk in cancer patients with bone disease.

Reference:

1. Farr JN et al. Blood 2014;123:647.

Disclosure Statement: Nothing to disclose.

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235

Ways to Cancer Counseling Centers: How do People Become

Aware of these Centers?

Melanie Schranz 1; Oliver Bayer 1; Margret Xyländer 2; Britta Büchler 1;

Silke Meier 3; Gudrun Bruns 4; Evelyn Flohr-Schmitt 5; Meike Achenbach 6;

Alexander Wünsch 7; Andreas Ihrig 8; Franziska Petridis 9; Larissa Rudolph 10;

Konstanze Pilgrim 11; Norbert Gelse 12; Thorsten Meyer 2; Susanne Singer 1

1Universitätsmedizin Mainz, IMBEI, Abt. Epidemiologie und

Versorgungsforschung, Mainz, Deutschland

2Universität Bielefeld - Fakultät für Gesundheitswissenschaften, Rehabilitative

Versorgungsforschung, Bielefeld, Deutschland

3Stiftung phönikks, Hamburg, Deutschland

4Tumor-Netzwerk Krebsberatung im Münsterland e.V. , Münster, Deutschland

5Psychosoziale Krebsberatungsstelle Würzburg, Würzburg, Deutschland

6Psychosoziale Krebsberatungsstelle Frankfurt, Frankfurt am Main, Deutschland

7Uniklinik Freiburg, Psychosoziale Krebsberatungsstelle Freiburg, Freiburg,

Deutschland

8Psychosoziale Krebsberatungsstelle Nordbaden, Heidelberg, Deutschland

9Psychosoziale Beratungsstelle der AWO, Karlsruhe, Deutschland

10Universitätsklinikum Leipzig, Abt. Medizinische Psychologie und Medizinische

Soziologie, Leipzig, Deutschland

11Psychosoziale Krebsberatungsstelle Nürnberg, Nürnberg, Deutschland

12Psychosoziale Krebsberatungsstelle Tübingen, Tübingen, Deutschland

Purpose: Cancer counseling centers (in German: Krebsberatungsstellen –

KBS) oer psychological and social (legal) support for patients and their

relatives who are confronted not only with physical but also with psycho-

social burdens as a result of cancer [1]. But how are people made aware

of such places?

Methods: Guideline-based interviews were used in a Germany-wide

qualitative study. 43 patients and relatives were interviewed face-to-face

by trained sta in 10 cancer counseling centers; 30 referring physicians

were interviewed via telephone by the project team. All interviews were

transcribed and evaluated by content analysis [2].

Results: Flyers and information brochures are important sources that

draw the attention of patients and their relatives to KBS. Websites, news-

paper advertisements, and information events were also mentioned. In

addition to public relations work, the personal approach - above all in the

medical care system, but also in the non-clinical and social environment

- was of central importance. Sometimes the referring physicians contact-

ed the KBS directly. Sometimes they even contacted the KBS directly on

behalf of the patients who were clearly struggling. Some physicians ad-

dress KBS routinely, while others only do so when an explicit need arises

(when those seeking advice are (very) burdened and express an increased

psychosocial (legal) counseling need). Disseminated in the medical/clini-

cal care system. As a result, closer cooperation with general practitioners,

social workers, and psychologists should be sought. Informative yers and

brochures can sharpen the focus on KBS and highlight the features that

distinguish it from other outpatient care services. Good public relations

are essential.

References:

1. Giesler JM et al. (2015) Ambulante psychoonkologische Versorgung durch

Krebsberatungsstellen – Leistungsspektrum und Inanspruchnahme durch

Patienten und Angehörige. Psychother Psych Med 65(12): 450-458.

2. Mayring P (2016) Einführung in die Qualitative Sozialforschung, Beltz.

Disclosure Statement: None of the authors have anything to disclose.

241

Spiritual Care in Oncology: Patients’ Perceived Spiritual

Support and Professionals’ Perceived Responsibility to Care

for their Patients´ Spiritual Needs – Data from a Pilot Project

Arndt Büssing 1; Eckhard Frick Sj 2; Jens Büntzel 3

1Professorship Quality of Life, Spirituality and Coping, Institute of Integrative

Medicine, Witten/Herdecke University, Herdecke, Deutschland

2Research Unit Spiritual Care, Clinic for Psychosomatic Medicine and

Psychotherapy, Technical University Munich, München, Deutschland

3Department of Otolaryngology, Palliative Care Unit, Südharz Clinic

Nordhausen, Nordhausen, Deutschland

Purpose: As part of the AG PRIO project on spiritual needs of cancer

patients and spiritual care competences of oncology sta we intended to

analyze the spiritual-religious (S/R) self-categorization of patients and

their health professionals.

Methods: Cross sectional survey in a dened time frame among patients

with cancer from treatment centers in East and West Germany and their

treatment team (i.e. physicians, nurses, psychologists, medical assistants)

with standardized questionnaires.

Results: We analyzed data from 171 patients (62% women; 61±12 years

of age) and from 78 health professions (78% women; 43±11 years of age;

35% physicians, 18% nurses, 47% other; 33% oncology wards, 36% hospi-

tals, 22% university hospital, 8% other). While a majority of sta regarded

themselves as religious and/or spiritual (41% R+S+, 11% R+S-, 9% R-S+,

39% R-S-), most patients stated to be non-religious (16% R+S+, 23% R+S-,

8% R-S+, 53% R-S-). ere were no signicant dierences between East

and West German centers. Among the sta, 33% of S/R and 79% of R-S-

(p<0,001; Chi2) do not feel responsible to care for spiritual issues. Never-

theless, 75% of S/R and 57% of R-S- patients (p=0,056; Chi2) felt supported

in their spiritual needs by the sta.

Conclusions: Health professionals´ and patients´ self-perception of being

spiritual/religious or not diers. is may have an impact on what patients

expect from the sta and how these may respond to their patients´ spiritu-

al needs. Even in widely secularized societies, patients may be aected by

unmet spiritual needs and unresponsive caregivers.

Disclosure Statement: e study was supported by a grant of German Cancer

Society. e authors disclose any conict of interest.

251

PACC: Patient Centered Care

Nicole Erickson 1; Carina Eckhardt 1; Lena Storck 2; Ingrid Ricard 1;

Anita Joos 2; Lian Liu 1; Peter E. Ballmer 2, 3; Friederike Mumm 4;

Christoph Riese 5; Volker Heinemann 1; Theres Fey 1

1 Ludwig Maximilian‘s University, Krebszentrum – CCC MünchenLMU –

Comprehensive Cancer Center, München, Deutschland

2Kantonsspital Winterthur, Department for Medicine, Winterthur

3Zürcher RehaZentrum, Davos-Clavadel, Schweiz

4 Ludwig Maximilian‘s University, Interdisziplinäres Zentrum für Psycho-

Onkologie, München, Deutschland

5CANKADO Service GmbH, Köln, Deutschland

Purpose: Investigation of ecacy of nutrition-related patient reported

outcomes (NR-PRO) and their implications in clinical care.

Methods: Multicenter, multinational trial exploring the acceptability,

perception, and usability of NR-PRO factors assessed using CANKADO’s

E-health platform.

Results: 188 patients undergoing treatment for gastrointestinal tumors in

Germany and Switzerland were asked to complete 79 tablet-based ques-

tions consisting of 2 validated questionnaires related to nutrition status

along with questions pertaining to acceptability. 34 Patients (18%) chose

not participate.152 patients (median age 62 years; range 22-86) were will-

ing to complete the questionnaires. While 84% perceived the tablet-based

questionnaire to be not dicult, older patients tended to nd the tab-

let-based format more unwieldy than younger patients (p=0.052). While

age was similarly distributed between the sexes, men were signicantly

more likely to require help completing the questionnaires than women

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(p=0.035). A high proportion (89%) largely, or completely, agreed that

NR-PROs via tablet should be integrated in routine clinical care.

Conclusions: Routine assessment of NR-PROs via tablet is an acceptable

approach for patients undergoing treatment for gastro-intestinal tumors

and poses a simple and ecient solution for integrating these valuable

assessment parameters into routine clinical care.

References:

1. Gotay C. et al. e prognostic signicance of Patient-Reported Outcomes in

cancer clinical trials. JCO Volume 26 (8) 2008.

2. Erickson N. et al. Tri-country translation, cultural adaptation, and validity

conrmation of the Scored Patient-Generated Subjective Global Assessment.

Support Care Cancer. 2019; 27(9):3499-350

Disclosure Statement: C.Riese is employed by Cankado.

252

On-Site Integrative Oncology: The Bochum/Hattinger Model

André-Michael Beer 1, Stefanie Nöpel-Dünnebacke 2, Birke Müller 1

1Klinik für Naturheilkunde, Klinik Blankenstein, Hattingen, Katholisches Klinikum

Bochum GmbH, Hattingen, Deutschland

2Klinik für Hämatologie, Onkologie, Palliativmedizin, St. Josef-Hospital, Klinikum

der Ruhr-Universität Bochum, Bochum, Deutschland

Purpose: For the last 10 years, the Clinic for True Naturopathy in Hat-

tingen-Blankenstein has oered a consultation service for integrative

oncology tot he St. Josef-Hospital. Ruhr-University Bochum, department

of hematology and oncology. Since February 2019, aregular consultation

service on site, twice weekly, has been conducted.

Methods: From the 20th of February to the 26th of September, 2019,

N=154 male and female patients from the department of hematology and

oncology, St. Josef Hospital, Ruhr-University Bochum, were treated. e

diagnoses were: Pancreatic carcinoma (N=81), Breast carcinoma (N=7),

Lung carcinoma (N=12), Eophageal carcinoma (N=10), Stomac carci-

noma (N=2), Colon and Rectalcarcinoma (N=17), Ovarian carcinoma

(N=3), Others (N=22). In addition to a therapy program consisting of

the classical European natural healing remedies, to include phytotherapy,

wraps compresses and cupping therapy, acupuncture and mistletoe thera-

py (N=26) were also oered to suitable patients.

Results: First indications show that more patients can be recruited during

oncological patient visits by the presence of a qualied doctor of true na-

turopathy, thereby promoting the possibility for complementary naturo-

pathic treatment such as mistletoe therapy. In this period, mistletoe ther-

apy was discussed with N = 26 patients. Finally, N = 8 patients performed

mistletoe therapy.

Conclusions: Consultation between the oncologist and a medical special-

ist of true naturopathic treatment would identify suitable patients. e

therapy concept o he Bochum/Hattinger model is herewith presented.

Disclosure Statement: None

256

A Comparison of Physical Activity Change Patterns and

Determinants between Breast, Prostate and Colorectal Cancer

Patients

Johanna Depenbusch 1, 2; Alexander Haussmann 1, 3; Angeliki Tsiouris 4, 5;

Laura Schmidt 3; Silke Hermann 6; Monika Sieverding 3;

Joachim Wiskemann 4; Nadine Ungar 3; Karen Steindorf 1

1Abteilung Bewegung, Präventionsforschung und Krebs, Deutsches

Krebsforschungszentrum (DKFZ) und Nationales Centrum für

Tumorerkrankungen (NCT), Heidelberg, Deutschland

2Medizinische Fakultät Heidelberg, Universität Heidelberg, Heidelberg,

Deutschland

3Psychologisches Institut, Universität Heidelberg, Heidelberg, Deutschland

4Abteilung Medizinische Onkologie, Nationales Centrum für

Tumorerkrankungen (NCT) und Universitätsklinikum Heidelberg, Heidelberg,

Deutschland

5Klinik für Psychosomatische Medizin und Psychotherapie, Universitätsmedizin

der Johannes Gutenberg-Universität Mainz, Mainz, Deutschland

6Epidemiologisches Krebsregister, Deutsches Krebsforschungszentrum (DKFZ),

Heidelberg, Deutschland

Purpose: Despite well-established benets of physical activity (PA) for

cancer patients, a majority of patients do not meet recommended PA

guidelines (≥150 min moderate-to-vigorous PA/week). e purpose

of the study was to investigate how PA behavior changed from pre- to

post-diagnosis, which sociodemographic and medical factors were asso-

ciated with PA and how change patterns and determinants of PA diered

between breast, prostate and colorectal cancer patients.

Methods: In a cross-sectional study, 912 cancer patients (457 breast, 241

prostate, 214 colorectal cancer; on average 15.1 months post-diagnosis)

completed a questionnaire assessing sociodemographic and medical vari-

ables as well as their weekly duration of PA pre-diagnosis and within the

last week. PA change patterns and dierences between cancer types were

analyzed with non-parametric tests. Logistic regression analyses were

used to identify sociodemographic and medical determinants of sucient

post-diagnosis PA. Additionally, population subgroups more or less likely

to be physically active were detected using classication tree analyses.

Results: Despite a modest decrease of PA from pre- to post-diagnosis,

we found that 54% of cancer patients indicated to be suciently active

post-diagnosis. Considerable dierences in pre-diagnosis PA between

cancer types disappeared post-diagnosis. While for all cancer types,

post-diagnosis PA was strongly aected by pre-diagnosis PA, we detect-

ed dierences between cancer types regarding further PA determinants.

Our results suggest that previously inactive prostate cancer patients and

recently diagnosed patients currently undergoing cancer treatment had an

increased likelihood of being insuciently active post-diagnosis.

Conclusions: e number of suciently active cancer patients was en-

couragingly high. Yet it seems important to further raise awareness of PA

in the general population as well as in the post-diagnosis setting, where

interventions that are more tailored to specic patient and cancer charac-

teristics need to be established.

Disclosure Statement: e study was funded by German Cancer Aid. ere is no

conict of interest.

Prof. Dr. Karen Steindorf gibt folgende Verbindungen außerhalb des eingereichten

Abstracts an:

Personal fees from Pzer Pharmaceuticals (Consulting for writing a brochure on

physical activity and cancer for breast cancer patients), personal fees from Adviva

Heidelberg (Lecture Fee), non-nancial support from Asklepios Clinics (Travel

costs), personal fees from BIG direkt health insurance (Lecture fee, travel costs),

personal fees from TEVA Pharmaceuticals (Lecture fee, travel costs).

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294

Safety of a Combined Supervised and Home-Based Whole-

Body Vibration Intervention for Childhood Cancer Survivors

Vanessa Oschwald 1; Aram Prokop 2; Sarah Otten 1; Volker Maas 2;

Fiona Streckmann 1, 3; Wilhelm Bloch 1; Jonas Krumbach 1;

Julia Däggelmann 1

1Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule

Köln

2Kinderkrankenhaus Amsterdamer Straße, Kliniken der Stadt Köln gGmbH

3Departement für Sport, Bewegung und Gesundheit, Universität Basel

Purpose: To assess safety of a whole-body vibration (WBV) intervention,

combining supervised and home-based training for childhood cancer

survivors.

Methods: Eight childhood cancer survivors (mixed cancer types, age:

6-17) participated in a 12-week WBV-intervention, comprising one super-

vised and two home-based sessions per week. Training was performed on

a side-alternating vibration platform. WBV-protocol included one warm-

up (60 sec, 18 Hz, 2mm peak-to-peak amplitude) and 5-10 progressive

training exercises (60-90 sec, 18-27 Hz, 2mm peak-to-peak amplitude).

Adverse events leading to health deterioration and intervention drop out

were evaluated. Side eects of WBV were secondarily investigated.

Results: No study dropout due to WBV-related adverse events occurred.

ree patients reported pain in the feet following WBV (vibration fre-

quencies: 22Hz and 27 Hz) that required early training stop or temporary

training interruption. Itching in the feet and legs during exercising was

reported in almost all patients. One patient experienced itching in the

lower back.

Conclusions: Not only supervised1 but also home-based WBV is safe for

childhood cancer survivors. However, close monitoring seems necessary

to detect the onset of pain. Survivors and families should be informed that

common symptoms of WBV like itching2 are possible during or immedi-

ately following WBV.

References:

1. Rustler V, Prokop A, Streckmann F, et al. Whole-Body Vibration Training

Designed to Improve Functional Impairments Aer Pediatric Inpatient Anti-

cancer erapy: A Pilot Study. Pediatr Phys er 2018;30(4):341-394

2. Rittweger J, Beller G, Felsenberg G. Acute physiological eects of exhaustive

whole-body vibration exercise in man. Clin Physiol 2000;20(2):134-142

Disclosure Statement: No conicts to disclosure.

303

Real-World Evidence of the Eectiveness and Safety of

NEPA (Netupitant-Palonosetron) for the Prevention of

Chemotherapy-Induced Nausea and Vomiting (CINV)

in Patients (PTS) Receiving Highly (HEC) or Moderately

Emetogenic Chemotherapy (MEC): Final Results of a German

Prospective Non-Interventional Study

Meinolf Karthaus 2, Peter Klare 3, Gülten Oskay-Özcelik 4, Volker Heilmann 5,

Elke Wierick 6, Pia Wülng 7, Carsten Hielscher 8, Dagmar Guth 9,

Mark-Oliver Zahn 10, Claus Hanusch 11, Joachim Hesse 12, Peter Jungberg 13,

Christian Kurbacher 14, Ute Neef 15, Jörg Schilling 16

1Hämatologie und Onkologie, Klinikum Neuperlach, München, Deutschland

2Städtisches Klinikum München Neuperlach, München, Deutschland

3Praxisklinik Krebsheilkunde für Frauen/Brustzentrum , Berlin, Deutschland

4Praxisklinik Krebsheilkunde für Frauen/Brustzentrum, Berlin, Deutschland

5Praxis Günzburg, Günzburg, Deutschland

6Gynäkologisch Onkologischer Schwerpunkt Lohsa, OT Weißkollm, Deutschland

7Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg, Deutschland

8g.SUND Gynäkologie Kompetenzzentrum, Stralsund, Deutschland

9Gynäkologische Praxis Plauen, Plauen, Deutschland

10Onkologische Kooperation Harz, Goslar, Deutschland

11Rotkreuzklinikum München Frauenklinik, München, Deutschland

12Praxis für Innere Medizin, Parchim, Deutschland

13Praxisklinik / Brustzentrum Chemnitz, Chemnitz, Deutschland

14Gynäkologisches Zentrum Bonn-Friedensplatz, Bonn, Deutschland

15Gemeinschaftspraxis für Innere Medizin, Hämatologie, Onkologie und

Gastroenterologie, Halle (Saale), Deutschland

16Praxisklinik / Brustzentrum Berlin, Berlin, Deutschland

Purpose: NEPA, the xed combination antiemetic composed of a neuroki-

nin-1 receptor antagonist (RA; netupitant) and a 5-hydroxytryptamine-3

RA (palonosetron), is recommended for CINV prophylaxis for HEC and

MEC. is prospective non-interventional study assessed quality of life

(primary endpoint), eectiveness and safety (secondary endpoints) of

NEPA in HEC/MEC-treated pts under real-world conditions. Here, we

report nal eectiveness and safety data by chemotherapy (CT) group.

Methods: Adult pts treated with 1- or 2-day (d) HEC or MEC receiving

NEPA per SmPC were enrolled. Eectiveness, including frequency and

severity of nausea and vomiting and use of rescue medication (RM), was

reported in pt diaries. Complete response (CR) was dened as no emesis

and no RM, and non-signicant nausea (NSN) as no or mild nausea. Ad-

verse events (AEs) were reported on d1–21 of each cycle (C). All data were

collected for 3 consecutive CT Cs.

Results: From 9/15 to 9/17, 2405 pts initially assessed at 162 centers across

Germany, of whom 2173 were analyzed. Median age was 58 y (range 25-

89); 85% were female and half of the pts had an ECOG of 0-1. Pts were

diagnosed with breast (66%), gastrointestinal (10%), ovarian (7%) or lung

(5%) cancer. More than half of the pts (1230, 56%) received anthracycline/

cyclophosphamide-(AC), 19% carboplatin-, 8% cisplatin-, 7% oxaliplatin-

and 9% other CTs. During the overall period in C1, CR rates were between

81-84% and comparable in the pt groups treated with dierent HEC or

MEC. NSN rates varied between over 73% in the carboplatin-, cisplatin-

and 45% in the oxaliplatin pt group, in the overall period in C1. Outcomes

were similar for C2 and C3. Overall, 7% of pts reported drug-related AEs,

with the most common (in >1% pts) being constipation, fatigue, insom-

nia, and nausea.

Conclusions: NEPA was highly eective at CINV control under re-

al-world conditions in AC-, carboplatin-, cisplatin-, oxaliplatin- and other

CT pts, with a predictable and favourable safety prole.

Disclosure Statement: Advisory Role, Honoraria: RIEMSER Pharma GmbH,

Helsinn Healthcare SA.

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313

Eects of a Whole-Body Vibration Intervention in Children

and Adolescents after Inpatient Anticancer Therapy on Ankle

Dorsiexion Function and Balance Control

Sarah Otten 1; Aram Prokop 2; Vanessa Oschwald 1; Volker Maas 2;

Fiona Streckmann 1, 3; Wilhelm Bloch 1; Jonas Krumbach 1;

Stefanie Willibald 1; Julia Däggelmann 1

1Institut für Kreislauorschung und Sportmedizin, Deutsche Sporthochschule

Köln, Köln, Deutschland

2Kinderkrankenhaus Amsterdamer Straße, Kliniken der Stadt Köln gGmbH, Köln,

Deutschland

3Departement für Sport, Bewegung und Gesundheit, Universität Basel, Basel,

Schweiz

Purpose: Ankle dorsiexion (DF) function (strength, range of motion

(ROM)) and balance control are oen impaired in children and adoles-

cents aer inpatient anticancer therapy. However, adequate functional ca-

pacity of the lower limbs is prerequisite for mobility and for being active

in general. Whole-body vibration (WBV) aims to improve those variables.

Methods: Eight children aer inpatient anticancer therapy (mixed diag-

noses, age: 6-17) participated in a twelve-week WBV intervention. Train-

ing was oered three times a week (1x supervised, 2x home-based). Train-

ing was performed on a side-alternating vibration platform. e training

sessions included one warm-up (60 sec, 18 Hz, 2mm peak-to-peak ampli-

tude) and 5-10 progressive training exercises (60-90 sec, 18-27 Hz, 2mm

peak-to-peak amplitude). Two testings were performed before and aer

the intervention assessing balance control (one-leg stance), ankle dorsi-

exor strength (hand-held dynamometry) and active DF ROM (measured

with bent and straight legs, goniometry).

Results: Positive trends were reported in balance control, strength of an-

kle DF and active ankle DF-ROM with straight legs. Active DF-ROM with

bent legs was signicantly improved.

Conclusions: e results indicate that our WBV-intervention, combin-

ing supervised and home-based training sessions, can improve all of the

three focused parameters, especially active DF-ROM. Consequently, the

barriers for a regained higher level of physical activity can be consider-

ably reduced. WBV might be a promising modality to improve lower limb

function in pediatric oncology.

Disclosure Statement: e authors have no conicts to disclosure.

314

Lung Cancer Patients’ Expectations and Support Needs

Regarding Patient Navigation

Hella Fügemann 1; Ute Goerling 2; Kathrin Gödde 3; Nina Rieckmann 3;

Jacqueline Müller-Nordhorn 4; Christine Holmberg 5

1Institut für Public Health, Charité – Universitätsmedizin Berlin, Berlin,

Deutschland

2Charité Comprehensive Cancer Center , Charité – Universitätsmedizin Berlin,

Berlin

3Institut für Public Health, Charité – Universitätsmedizin Berlin, Berlin

4Bayerisches Krebsregister, Bayerisches Landesamt für Gesundheit und

Lebensmittelsicherheit

5Institut für Sozialmedizin und Epidemiologie, Medizinische Hochschule

Brandenburg Theodor Fontane

Purpose: Lung cancer patients face a low ve-years-survival rate.1 Due

to this poor prognosis, treatment with palliative intent is oen initiated

early aer diagnosis. Navigation programs for patients aim to optimize the

individual’s care trajectory including early integration of palliative care,

which has positive eects on patients’ quality of life.2 In Germany, there is

little coordination of a patient`s continued care and patient navigation is

only slowly evolving. In this study, we investigated lung cancer patients`

perspectives on patient navigation.3

Methods: A longitudinal interview study was conducted with 20 lung

cancer patients assessed at three time points (aer diagnosis, at 3-6 and at

6-12 months). e interviews were audio-recorded and transcribed verba-

tim. We conducted a thematic analysis.

Results: Navigation needs were mainly seen in emotional and practical

support, but also in linking patients to existing support services and pro-

viding information on social care issues. Patients would appreciate the

continued support through one contact person. For navigation to be of in-

terest to patients its implementation within existing care structures, such

as the outpatient clinic or oncology practice, is crucial.

Conclusions: From the patients` perspectives, navigation could be a sup-

portive approach to identify and address their individual healthcare needs

and improve their journey through the complex care continuum by hav-

ing one permanent contact person.

References:

1. Krebs in Deutschland 2013/2014: Robert Koch-Institut, GEKID e.V.,

2017

2. Temel JS, et al. Early palliative care for patients with metastatic non-small-cell

lung cancer. N Engl J Med 2010

3. Fügemann H, et al. Patienten-Navigation – Erwartungen, Bedarfe und Anfor-

derungen aus Patientenperspektive. DKVF. Berlin 2019

Disclosure Statement: is work is part of the research consortium

“NAVICARE – Patient-oriented health services research”. NAVICARE is

funded by the German Ministry of Education and Research (01GY1601).

316

Patient Information, Communication and Competence

Empowerment in Oncology (PIKKO) – Evaluation of a

Supportive Care Intervention for Overall Oncological Patients:

Baseline Data and Representativeness

Nico Schneider 1; Anna Bäcker 1; Katja Brenk-Franz 1; Christian Keinki 2;

Jutta Hübner 3; Florian Brandt 4; Geraldine von der Winkel 4; Lutz Hager 5;

Bernhard Strauß 1; Uwe Altmann 1

1Institut für Psychosoziale Medizin und Psychotherapie, Universitätsklinikum

Jena, Jena, Deutschland

2Deutsche Krebsgesellschaft, Berlin, Deutschland

3Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum

Jena, Jena

4IKK Südwest, Saarbrücken, Deutschland

5ze:roPraxen, Schwetzingen, Deutschland

Purpose: In Saarland the supportive new consulting and information

path, called PIKKO (funded by InnoFond, 01NVF17011), is implemented

for all types of cancer. e evaluation study is still ongoing. e study

design is presented, the participating patients are described and their rep-

resentativeness discussed.

Methods: We included all cancer types (new diseases and existing ones)

and used a non-randomized, comparative, multicenter superiority design.

e patients assigned to a control group (usual care) or intervention group

(usual care + PIKKO). e core elements of intervention are a patient nav-

igator, oncological knowledge database, and specialized psycho-oncolog-

ical counseling. In addition to patient surveys, data from statutory health

insurances and usage data from the web database are collected, and inter-

views with patient navigators and doctors are carried out.

Results: Recruitment will be completed in October 2019. Preliminary de-

mographic analyzes indicated that the PIKKO sample is broadly similar to

other German cancer studies [1, 2, 3]. e score ranges for quality of life,

depression and anxiety are comparable to Gotze [1] and Sauer [2], but a

little more distressed. Dominant cancer types are breast cancer (C50), leu-

kemia and lymphoma (C81-C96) and lung cancer (C33-C34). Final data

will be available at time of the congress.

Conclusions: PIKKO is designed to improve quality of life, self-ecacy,

health literacy and patient satisfaction and to reduce psychological dis-

tress, related health care costs and the days of inability to work.

References:

1. Gotze H. [Psychosocial Situation and Patient Satisfaction among Clients of

Cancer Counselling Centers in Saxony]. Psychother Psychosom Med Psychol

2016.

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2. Sauer Cl. Impact of social support on psychosocial symptoms and quality of

life in cancer patients … Acta oncologica 2019.

3. Hartung TJ. e risk of being depressed is signicantly higher in cancer pati-

ents than in the general population... Eur J Cancer 2017.

Disclosure Statement: No competing interests.

321

Assessment of Body Composition with Dierent Methods in

Breast Cancer Patients

Monika Reuss-Borst 1, 2; F. Joos 2; U. Kämmerer 3

1Rehabilitation-Center Bad Bocklet, Deutschland

2University of Göttingen

3Dpt. Of Gynecology and Obstetrics, University of Würzburg

Purpose: Many studies have consistently shown that malnutrition is asso-

ciated with higher degrees of treatment-related toxicity, reduced response

to cancer treatment and worse prognosis. In particular, body mass index

may be normal in patients with sarkopenic obesity. So far, screening for

malnutrition, in particular the assessment of body composition is still the

exception in daily practice although dierent well-established techniques

of body composition analysis do exist.

Methods: In this study body composition of 92 breast cancer patients was

analyzed at t0 and aer 20 weeks. Dierent methods such as bioelectri-

cal impedance analysis (BIA), near-infrared interactance (NIR) and dual

x-ray absorptiometry (DXA) (considered as the current gold standard) as

well as a simple body fat scale (BFS) from the discounter were compared

with respect to various outcome variables (e.g. fat mass (FM), fat free mass

(FFM) etc.), their validity and reliability as well as costs and handling.

Results: DXA, BIA and NIRS yielded similar results for body compo-

sition, including FM (DXA: 28,9 BIA: 28,2 kg, NIRS: 27,9kg) and FFM

(DXA: 44,5kg, BIA: 46,2kg, NIRS: 46,5kg). Results, however, diered sig-

nicantly between these 3 methods and a simple BFS (FM: 22kg, FFM:

50,0kg), which overestimated fat free mass and underestimated fat mass

(p<0,01). With regard to changes in body composition over time, all 4

investigated methods yielded comparable results (FM p=0,698 resp. FFM

p=0,211).

Conclusions: All investigated methods are suitable for follow-up checks

in oncological patients when monitoring changes in body composition

over time. is even applies for a simple body fat scale which, however,

signicantly overestimates FFM and underestimates FM in comparison

to the other techniques. For the exact measurement of body composition

NIR and BIA are rapid, safe, non-invasive and inexpensive techniques

with valid and reliable results - ideal for routine body composition as-

sessment.

338

Physical Fitness and Body Composition in Breast Cancer

Patients that Adhere to Dierent Nutritional Regimes

Monika Reuss-Borst 1, 2; T. Schäfer 2; U. Kämmerer 3

1Center for Rehabilitation and Prevention Bad Kissingen/Bad Bocklet

2University of Göttingen

3Dept. of Obstetrics and Gynecology, University of Würzburg

Purpose: Breast cancer (BC) patients are oen advised to adhere to a

“healthy diet”. However, this diet has not been dened yet. e aim of this

study was to evaluate the eect of three dierent diets on physical tness

and body composition.

Methods: 152 BC patients could choose between 3 diets. ey received in-

tense training and advice during 3 wks of rehabilitation and were instruct-

ed to adhere to their diet for 20 weeks in total. Proportion of macronutri-

ents in energy percent (fat/protein/carbohydrates) were: Ketogenic diet

(KD) 80/16/4 (n = 29), Low-Carb diet (LC) 50/20/30 (n = 92) and western

diet (WD) 30/15/55 (n = 31). Dual-Energy x-ray (DXA) and spiroergom-

etry were performed at start (t0) and aer 20 weeks (t20) to analyse body

composition and physical tness. Data were analyzed by non-parametric

Kruskal-Wallis test or Mann-Whitney-U-Test.

Results: From t0 to t20 muscle/fat ratio increased [2.1/2.4 (KD), 1.6/1.77

(LC) (p=0.02) and 1.65/1.75 (WD)] and visceral fat decreased [10.0/7.9kg

(KD), 14.3/12.6kg (LC) and 12.7/12.1 (WD)] in all diet groups. At t0, to-

tal fat was lowest with KD (21.8kg) (p<0.001) and the muscle/fat relation

(2.3) was signicantly higher than with LC (1.8) and WD (1.9). Subgroup

analysis based on food questionnaires revealed, that 14/31 patients had

used KD, 8/31 LC and only 7/31 WD before the study while 14/92 in the

LC group hat used LC before and the 31/31 patients of the WD group

started from WD.

With regard to physical tness, both, Vo2/kg at VT2 (anaerobic

threshold) [KD (+2.93), LC (+0.64) and WD (+0.48]) and Vo/kg Max [KD

(+2.51), LC 1.43 and WD(+2,49)] increased between t0 and t20.

Conclusions: All 3 groups improved in body composition and physical

tness attesting the ecacy of the rehabilitation intervention. However,

KD proved to be best for positive changes in muscle/fat ratio and physical

tness. One reason of this surprising result might be that ketone bodies

may act as “super fuel” improving energy eciency which is especially

important in cancer patients.

e therapeutic potential of a KD as nutritional regime should be fur-

ther evaluated.

390

Phytotherapeutic Approaches for Treating Mucositis, Loss of

Appetite, Xerostomia and Ageusia –An Analysis of Empirical

Knowledge

Judith Büntzel 1; Christoph Bauer 2; Jens Büntzel 3

1Klinik für Hämatologie und Onkologie, Universitätsmedizin Göttingen,

Görringen, Deutschland

2Medizinische Klinik III, Klinikum Fulda, Fulda, Deutschland

3Klinik für HNO-Erkrankungen, Kopf-Hals-Chirurgie, Südharz-Klinikum

Nordhausen, Nordhausen, Deutschland

Purpose: Which empirical reports can be found regarding phytothera-

peutics used traditionally to treat lack of appetite and dysphagia?

Methods: We screened 10 German books on phytotherapy for the follow-

ing symptoms: mucositis/stomatitis/gingivitis, anorexia/loss of appetite,

xerostomia and loss of taste. All traditional European herbs were includ-

ed. Hits were registered on an Excel spreadsheet.

Results: We found 133 plants; 103 are recommended for treating oral mu-

cositis, 75 for stimulating appetite, 10 for alleviating xerostomia and for

stimulating taste. Matricaria chamomilla L., Salvia ocinalis L. and the

bark of Quercus robur L. are the most commonly mentioned herbs for

treating mucositis. e following herbals were the most frequently recom-

mended as stimulants of appetite: Artemisia absinthium L., Centaurium

Hill and Cichorium intybus L.. Zingiber ocinale Roscoe, Gentiana lutea

L. und Centaurium Hill were mentioned several times as potent agents to

alleviate xerostomia. Gentiana lutea L. might be also used to treat ageu-

sia. Gentiana lutea L. is qualied to treat all four symptoms investigated;

Angelica archangelica L., Zingiber ocinale Roscoe, Cuminum cyminum L.

and Centaurium Hill are recommended for treating three out these.

Conclusions: Here we summarize a canon of the 10 plants recommended

by traditional (European) medicine.Clinical studies are required to inves-

tigate their therapeutic ecacy against mucositis, anorexia, xerostomia

and ageusia.

Disclosure Statement: e authors declare no conict of interest.

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405

Reduction of Severity of Chemotherapy-Induced Peripheral

Neuropathy by Onlife: Final Results of the Breast Cancer

Cohort of the Stefano Trial

Matthias Zaiss 1; Jens Uhlig 2; M.-O. Zahn 3; Thomas Decker 4;

Helmar Lehmann 5; Johanna Harde 6; Cathrin Hogrefe 6; Corinne Vannier 6;

Norbert Marschner 1, 6

1Praxis für interdisziplinäre Onkologie & Hämatologie GbR, Freiburg im

Breisgau, Deutschland

2Praxis Dr. med. Jens Uhlig, Naunhof, Deutschland

3Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation

Harz, Goslar, Deutschland

4Studienzentrum Onkologie Ravensburg, Ravensburg, Deutschland

5Universitätsklinikum Köln (AöR), Köln, Deutschland

6iOMEDICO AG, Freiburg im Breisgau, Deutschland

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a

common and potentially dose-limiting side eect of neurotoxic chemo-

therapy, especially of platinum and taxanes, with a profound impact on

patients (pts)’ quality of life and survivorship. It is predominantly caused

by sensory axon damage. ere is no eective strategy to prevent or cure

CIPN. OnLife®, a patented mixture of fatty acids (F.A.G.®) with the main

component palmitoylethanolamide (PEA), is supposed to have anti-in-

ammatory, neuroprotective and antinociceptive properties.

Methods: STEFANO is an observational, prospective, two-cohort, mul-

ticenter study designed to evaluate the inuence of OnLife® on existing

CIPN in adult pts with colon or breast cancer aer neo-/adjuvant che-

motherapy (cohort A: colon cancer, oxaliplatin-based therapy; cohort B:

breast cancer, paclitaxel therapy). Pts received OnLife® orally BID for 3

months. Neuropathy assessment before, during and aer OnLife® intake

included physical examination and neurophysiological testing, i.e. tendon

reexes, vibration sensitivity and CIPN grading according to CTCAE

v4.03. e primary objective was the change in severity of CIPN (CT-

CAE v4.03) before and aer 3 months of OnLife® intake. Secondary end-

points included Patient-reported outcomes (PROs; EORTC QLQ-C30,

-CIPN20). Descriptive statistics were used to analyze data.

Results: In total, 74 breast cancer pts with paclitaxel-induced CIPN re-

ceived OnLife®. According to CTCAE, aer OnLife® intake 31% of pts had

an improvement of sensory CIPN, 54% of pts experienced a stabilization,

with no further worsening, 1% of pts had a deterioration and 14% of pts

were not evaluable. In pts with grade 2/3 sensory CIPN (n=58), 36% had

an improvement, 50% a stabilization and no deterioration occurred. Ac-

cording to PROs, 45% of pts had less symptoms and functional limitations

related to sensory CIPN aer OnLifeâ intake.

Conclusions: OnLife® may reduce the severity of existing CIPN in breast

cancer pts treated with paclitaxel and thus appears to be a promising treat-

ment option for CIPN.

458

Administration of Peglgrastim Prophylaxis Via Pre-Filled

Syringe (Neulasta®) or On-Body Injector (OBI): Interim

Results on Patient Preference and Health Economics from the

Convenience Study

Michael Metz 1; Dieter Semsek 2; Ulrich Hutzschenreuter 3; Thomas Fietz 4;

Johanna Harde 5; Stefan Zacharias 5; Gunther Rogmans 6;

Carsten Hielscher 7; M.-O. Zahn 8; Christiane Fichter 5; Sina Grebhardt 5;

Gerlinde Egerer 9; Karin Pottho 5

1OPS Göttingen, Göttingen

2Praxis für interdisziplinäre Onkologie & Hämatologie GbR, Freiburg im

Breisgau, Deutschland

3Hämatologisch-Onkologische Gemeinschaftspraxis, Hämatologisch-

Onkologische Gemeinschaftspraxis, Nordhorn, Deutschland

4Schwerpunktpraxis für Hämatologie und Internistische Onkologie,

Gastroenterologie, Singen (Hohentwiel), Deutschland

5iOMEDICO AG, Freiburg im Breisgau, Deutschland

6ZAGO - Zentrum für ambulante gynäkologische Onkologie, Krefeld,

Deutschland

7g.SUND Gynäkologie Kompetenzzentrum Stralsund, Stralsund, Deutschland

8Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation

Harz, Goslar, Deutschland

9Universitätsklinikum Heidelberg, Medizinische Klinik und Poliklinik V,

Heidelberg, Deutschland

Purpose: e eectiveness of granulocyte colony-stimulating factors

(G-CSFs) like peglgrastim depends on the optimal timing, recommend-

ed ≥24 h aer chemotherapy (CTx) according to SmPC and guidelines.

Return visits to the medical oce for peglgrastim administration, how-

ever, may be burdensome and cause additional expenditure of time and

costs for both, patients and medical sta.

e peglgrastim On-body injector (OBI) is a small injector automati-

cally delivering a subcutaneous peglgrastim dose aer 27 h without need

of return visit to the medical oce. erewith the OBI has the potential

to optimize peglgrastim prophylaxis. e CONVENIENCE study aims

to evaluate patient’s preference and health economics for peglgrastim

administration via OBI versus pre-lled syringe (PS) in real-world in

Germany.

Methods: In this randomized, multicenter study (partially funded by

AMGEN GmbH) 400 patients with early breast cancer receiving 2 or 3

weekly anthracycline/cyclophosphamide or 3 weekly taxane-based CTx

or patients with Non-Hodgkin lymphoma receiving 1st-line R-CHOP-14

or-21 will be enrolled at 50 sites in Germany. Patients are observed for

4 CTx cycles supported with peglgrastim OBI or PS in an alternating

sequence with 1:1 randomization of the application form to start with.

Patient’s preference and inuence of peglgrastim administration on daily

life and cost factors will be evaluated using patient surveys.

Results: For this prespecied interim analysis, 200 patients were random-

ized between 06/2018 and 01/2019. Data on patient characteristics, time

interval between CTx and peglgrastim administration, patient’s prefer-

ence before and aer study including reasons for decision and inuence of

the dierent application forms on daily life (daily routine, social life, time

restriction) and health economics will be presented.

Conclusions: e results of the interim analysis demonstrate the feasibil-

ity, eectiveness and convenience of administering peglgrastim via OBI.

Reference:

1. Metz M et al, DGHO 2019, P944.

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462

Motivation for an Active Lifestyle (Motiva) – Pilot Study of

a Behavior-Change Module in Exercise Programs for Cancer

Survivors

Melanie Glausch 1; Friederike Stölzel 1; Nadja Seidel 1; Anne Fetzer 1;

Vera Fieber 1; Bornhäuser Martin 1, 2, 3; Nadine Ungar 4; Joachim

Wiskemann 5

1Universitätsklinikum Carl Gustav Carus Dresden, Universitäts Krebscentrum

(UCC), Dresden, Deutschland

2Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und

Poliklinik I, Dresden, Deutschland

3Nationales Centrum für Tumorerkrankungen (NCT), Dresden, Deutschland

4Ruprecht-Karls-Universität Heidelberg, Psychologisches Institut

Genderforschung und Gesundheitspsychologie, Heidelberg, Deutschland

5Medizinische Onkologie, Universitätsklinikum Heidelberg, Nationales Centrum

für Tumorerkrankungen (NCT), Heidelberg, Deutschland

Purpose: Physical Activity (PA) is associated with many benets for

cancer survivors (CS).1 However, research has shown insucient levels

of PA for CS. Rehabilitation sport groups (RSG) are a common way to

deliver exercise interventions to CS in Germany but measures to increase

sustainability of PA aer the end of RSG are still lacking. erefore, the

National Center for Tumor Diseases (NCT)/UCC Dresden and the NCT

Heidelberg developed a behavior-change program (MotivA) as additional

module for existing RSG.

Methods: MotivA teaches behavior-change-techniques (e.g. action-plan-

ning and coping) based on the Health Action Process Approach. MotivA

is an additional module that can be used in CS groups. A project kit free

of charge consists of a manual for trainers (incl. a CD with 7 audio-inputs)

and a workbook for CS. A pilot-study with a pre-post-3 month-follow-up

(FU) design without control group investigates the eects of MotivA on

subjective PA, motivational determinants of PA and program acceptance

with 29 participants.

Results: 76% of the participants were pleased with the additional behav-

ior-change module being part of the exercise program. At baseline, 62% of

the participating patients reported insucient PA. Motivational barriers

as ‘Can’t pick myself up’ (47%), ‘Not in the mood’ (33%) and ‘Comfortable

at home’ (33%) and ‘Bad weather’ (32%), were most frequent. Pre-post

dierences show a signicant increase in subjective reported PA levels

(p<.01, r=.61) and a signicant decrease of motivational barriers (p < .01,

r = .49). e eects in increased subjective PA and reduced motivational

barriers remained stable at 3 months-FU.

Conclusions: e results of this pilot-study are promising that MotivA

can support CS in developing a more active lifestyle. MotivA can be easily

disseminated and integrated in any exercise program for CS.

Reference:

1. Christensen, J. F., Simonsen, C. & Hojman, P. (2018). Comprehensive Physio-

logy, 9(1):165-205.

Disclosure Statement: No conicts of interest.

494

Dening Criteria for Guiding Cancer Patients to Find a

Reputable Complementary Medicine Provider: Results of a

Mixed-Methods Study

Alize Rogge 1; Isabel Baur 2; Gabriele Blettner 3; Ulrike Holtkamp 4;

Markus Horneber 5; Patrick Jahn 6; Stefanie Joos 7; Silva Keberle 8;

Anita Kettelgerdes 9; David Klemperer 10; Alfred Längler 11; Petra Voiß 12, 13;

Joachim Weiß 14; Claudia Witt 1, 15, 16

1Charité Universitätsmedizin Berlin Campus Benjamin Franklin, Institute for

Social Medicine, Epidemiology, and Health Economics, Berlin, Deutschland

2Universität Zürich, Competence Center Medicine Ethics, Zürich, Schweiz

3Deutsche Krebshilfe, INFONETZ KREBS, Bonn, Deutschland

4Deutsche Leukämie- und Lymphom-Hilfe, Bonn, Deutschland

5Paracelsus Medizinische Privatuniversität Nürnberg, Department of Internal

Medicine, Nürnberg, Deutschland

6Universität Halle, Nursing Research Unit, Halle (Saale), Deutschland

7Universitätsklinikum Tübingen Medizinische Universitätsklinik, Institute for

General Practice and Interprofessional Health Care, Tübingen, Deutschland

8Eskamed AG, Basel, Schweiz

9TK Techniker Krankenkasse, Buchen, Deutschland

10Ostbayerische Technische Hochschule Regensburg (OTH Regensburg), Faculty

of Social and Health Sciences, Regensburg, Deutschland

11Gemeinschaftskrankenhaus Herdecke, Institute of Integrative Medicine,

Herdecke, Deutschland

12Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Clinic for Naturopathy and

Integrative Medicine, Essen, Deutschland

13Städtisches Klinikum Karlsruhe gGmbH, Gynaecology Clinic, Karlsruhe,

Deutschland

14Uniklinik Freiburg - Klinik für Tumorbiologie, Department of Psychooncology,

Freiburg im Breisgau, Deutschland

15Universität Zürich, Institute for complementary and Integrative Medicine,

Zürich, Schweiz

16University of Maryland School of Medicine Department of Neurology, Center

for integrative Medicine, Baltimore, United States

Purpose: Approximately half of cancer patients use complementary med-

icine(CM) during their cancer treatment[1]. However, even in cases of

positive evidence for CM therapies [2], it is still dicult for cancer pa-

tients to identify reputable CM providers on their own. e aim of this

study was to develop and evaluate a criteria list to provide guidance to

cancer patients seeking a reputable CM provider.

Methods: In this mixed-methods study, results of a systematic literature

review, a multi-level expert consensus procedure (n=15) and a practice

evaluation from three relevant stakeholder perspectives (cancer patients

(n=18), CM providers (n=26) and oncology physicians (n=20)) were

combined.

Results: A total of 30 CM criteria were extracted from the literature, and

12 more were added by the experts. All criteria were assigned in their

importance for cancer patients to nd reputable providers, oncology phy-

sicians to establish a CM provider network and registers for quality assur-

ance in nonmedical CM providers. A nal comprehensive list of 8 criteria

guiding cancer patients to nd a reputable CM provider was developed in

the form of a leaet.

Conclusions: Health professionals and cancer information services might

nd the criteria list helpful when aiming to strengthen patients’ awareness

of quality-related factors associated with nonmedical CM providers. e

criteria developed might support the development of standards for quality

assurance in CM in oncology.

References:

1. Horneber, M., et al., How many cancer patients use complementary and alterna-

tive medicine: a systematic review and metaanalysis. Integr Cancer er, 2012.

11(3): p. 187-203.

2. Lyman, G.H., et al., Integrative erapies During and Aer Breast Cancer Treat-

ment: ASCO Endorsement of the SIO Clinical Practice Guideline. J Clin Oncol,

2018. 36(25): p. 2647-2655.

Disclosure Statement: We declare no competing interests. is project is part of

the collaborative research project KOKON supported by the German Cancer Aid

[grant number 109863].

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An Interdisciplinary Outpatient Clinic for Patients with

Neurological Sequelae of Cancer Therapies – Results of a Pilot

Project at the University Hospital of Bonn

Johannes Weller1, Maria Vonnahme2, Martin Schumacher2, Judith Sirokay3,

Tobias Holderried2, Ulrich Herrlinger1, Niklas Schäfer1

1Universitätsklinikum Bonn, Sektion Neuroonkologie, Bonn, Deutschland

2Universitätsklinikum Bonn, Medizinische Klinik III (Onkologie), Bonn,

Deutschland

3Universitätsklinikum Bonn, Klinik für Dermatologie, Bonn, Deutschland

Purpose: Most patients with cancer experience adverse events aer on-

cological treatment. Neurological sequelae are among the most important

challenges in patient survivorship, including but not limited to muscle

weakness, neuropathic pain, gait disorders and cognitive impairment,

which oen have a signicant impact on activities of daily life. To improve

diagnosis and treatment of these side eects, we started a pilot project for

cancer patients with neurological symptoms.

Methods: A consultation service for cancer patients was on a trial basis

implemented at the Division of Clinical Neurooncology. Consultations

were requested via the clinical workstation used at a tertiary universitary

medical center. Necessary information was a short description of symp-

toms, the assumed diagnosis and the priority in time. Contact was also

possible by phone call of selected collaborators. Our experience of the pi-

lot project was analysed in a descriptive manner.

Results: Between October 2018 and July 2019, a total of 42 patients with

65 visits were evaluable. e most frequent question was dierentiation

between chronic gra-versus-host-disease and neuropathy or myopathy

(40,5%). e leading neurological diagnosis was peripheral neuropa-

thy (42,9%). In 76,2% of the cases the neurological consultation led to

additional examinations and in 71,4% of the cases the consultation had

therapeutic implications. Usage of antiepileptic drugs or antidepressants

to modify neuropathic pain was recommended in 16,7% of the cases. 17

patients had at least one follow up visit within the reported period. Suc-

cessful treatment with improvement of symptoms was shown in 35,3% of

patients with follow-up visits.

Conclusions: ere seems to be a formerly unmet demand of neurologi-

cal consultation service in neurological sequelae of cancer therapies that

can be supplied by a specialized outpatient clinic. Building on the expe-

rience of this pilot project, a special outpatient clinic will now be perma-

nently established at our Division of Clinical Neurooncology.

505

Onkoaktiv-Network Evaluation: A Patient’s Perspective

Annelie Voland; Joachim Wiskemann

Nationales Centrum für Tumorerkrankungen – NCT, Medizinische Onkologie,

Heidelberg, Deutschland

Purpose: More than 700 RCTs have shown signicant positive eects of

exercise interventions for cancer patients and survivors; as well as clinical

relevant decreases in mortality rates through exercise behavior 1. Howev-

er, there is no comprehensive provision of exercise therapy in the German

medical system. erefore, OnkoAktiv follows the idea of building a net-

work, consisting of exercise professionals, training- and cancer treatment

centers, to connect patients with quality assessed and certied exercise

oers. e purpose of the project was to evaluate the work of OnkoAktiv

from a patient’s perspective.

Methods: Patients are recruited through OnkoAktiv at the National Cen-

ter for Tumor Diseases in Heidelberg. Evaluation consists of three assess-

ment time points (Q1: patient´s rst consultation, Q2: completed con-

nection to training facility, Q3: 8 weeks of exercise therapy) measuring

QoL, self- ecacy, volume of exercise, satisfaction, structure and process

quality parameters of the OnkoAktiv service and supervision by exercise

professionals.

Preliminary Results: By now, 71 of 86 patients with an average age of 56

years (SD=11.52) are enrolled, of which 59 already completed Q1 and 25

Q3. e distribution presents 26 patients with breast-, 19 with prostate-

and 20 with other cancer types. e mean time for patient´s placement

in an exercise facility was 38 days, serving 37 dierent exercise facilities

within the Rhein-Neckar-Region. 35 out of 55 participants already report-

ed high satisfaction in rating the OnkoAktiv service; however training

volume seems to be demanding during treatment and needs to be adjusted

on a day to day basis. 14 patients dropped out aer enrolment. Recruit-

ment will be completed in Oct 2019, data analysis will be nalized Dec

2019.

Conclusions: is study is the starting point of the OnkoAktiv-network

evaluation for further research in the eld of oncological exercise therapy.

Reference:

1. Christensen et al. (2018): Exercise Training in Cancer Control and Treatment.

In: Comprehensive Physiology 9 (1), S. 165–205.

Disclosure Statement: None

536

Eects of Physical Activity on Sexual Dysfunction in

Urooncological Patients – A Systematic Review

Nadine Reimer 1; Rebecca Böwe 2; Freerk Baumann 1

1University of Cologne, University Hospital of Cologne, Department I of Internal

Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf,

Köln, Deutschland

2Hochschule Fresenius, Faculty of Health and Social, Köln, Deutschland

Purpose: Many therapies performed as part of cancer treatment cause

sexual dysfunction as a side eect, which can occur, for example, as impo-

tence (up to 57%) and impaired sexual desire (up to 78%). Data show that

a higher activity level in urooncological cancer patients is associated with

better sexual health. is systematic review aimed at demonstrating the

ecacy of exercise interventions for sexual dysfunction in urooncological

patients.

Methods: A systematic data search was performed in PubMed in May

2019. In addition, the reference lists of individual publications were

screened. e review was undertaken according to the Preferred Report-

ing Items for Systematic Reviews and Meta-Analyses (PRISMA) state-

ment.

Results: e current status of the paper may change until the Congress

in February 2020. e systematic review currently includes 24 studies (16

RCTs, 1 non-RCT, 4 single-arm trials, 1 interview, 1 case report, 1 case

series) involving approximately 1605 cancer patients. e studies involved

prostate cancer (20), endometrial cancer (1), cervical cancer (1), gynae-

cological cancer (1), gynaecological and other cancers (1). e exercise

interventions were performed individually or in combination with other

interventions such as electrostimulation, nutrition or cognitive training.

For prostate cancer, erectile and sexual function, potency, and libido im-

prove (partly signicantly) by performing pelvic oor muscle exercise

(PFME), resistance and aerobic exercise, yoga and penile vibratory stim-

ulation compared to control group. For women, PFME, Pilates, resistance

and aerobic exercise show (partly signicantly) positive eects on sexual

activity and sexual function.

Conclusions: e rst set of data shows positive eects of exercise inter-

ventions on urooncological patients. is requires further studies.

Reference:

with the main author

Disclosure Statement: ere are no conicts of interest.

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539

Patient Information, Communication and Competence

Empowerment in Oncology (PIKKO) – A Supportive Care

Intervention for Oncological Patients

Christian Keinki 1; Katrin Clauß 1; René Meyer 1; Annika Momberg 1;

Robert Terbach 1; Nico Schneider 2; Anna Bäcker 2; Florian Brandt 3;

Geraldine von der Winkel 3; Lutz Hager 4; Bernhard Strauß 2; Uwe Altmann 2;

Jutta Hübner 5

1Deutsche Krebsgesellschaft e.V., Projekt PIKKO, Berlin, Deutschland

2Universitätsklinikum Jena, Institut für Psychosoziale Medizin und

Psychotherapie, Jena, Deutschland

3IKK Südwest, Saarbrücken

4ze:roPRAXEN GbR, Schwetzingen, Deutschland

5Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Deutschland

Purpose: In German healthcare, cancer patients are faced with confusing

care structures and an inadequate integration of psychosocial and infor-

mative support services. For this reason, a new care concept, called PIKKO,

is tested in the Saarland.

PIKKO is a collaborative project which is funded by the Innovation

Fund. Consortium partners are German Cancer Society, Cancer Society

of the Saarland, University Hospital Jena, IKK Südwest, Techniker Kran-

kenkasse (TK), and Knappscha.

Methods: Core elements of PIKKO are patient navigators, which accom-

pany cancer patients on their way through their therapy. In addition,

patients can access quality-assured information at any time via an exclu-

sively created oncological knowledge database and can take advantage of

specialized psychosocial counselling services.

All cancer types were included. Patients were either assigned to a

control group (usual care) or intervention group (usual care + PIKKO).

We used patient surveys to evaluate all patient related outcomes. Health

care costs were analyzed with data from participating statutory health

insurances.

Results: Main goal is to empower patients to deal with their disease in

a well-informed and autonomous manner. In measurable terms, PIKKO

should lead to a better quality of life, self-ecacy, health literacy and sat-

isfaction with healthcare. At the same time there should be a reduction of

psychological stress and costs of care.

Overall 15 patient navigators were deployed. Recruitment of patients

for the control group is completed. e intervention group is recruiting

until March 2020.

Conclusions: PIKKO is intended to become a well-established and benet

assessed program which improves care of all cancer patients in Germany.

Disclosure Statement: No competing interests.

550

Safety and Eectiveness of Sensor-Controlled Scalp Cooling

to Prevent Chemotherapy-Induced Alopecia in Patients with

Ovarian and Other Female Genital Tract Cancers

Christian M. Kurbacher 1; Nele Kettelhoit 1; Susanne Herz 1;

Gabriele Kolberg 1; Claudia Schweitzer 1; Jutta Anna Kurbacher 2

1Gynäkologisches Zentrum Bonn-Friedensplatz, Bonn

2Gynäkologisches Zentrum Bonn-Friedensplatz, Gynäkologie II (Allgemeine

Gynäkologie und Geburtshilfe), Bonn

Purpose: In prospective clinical trials, sensor-controlled scalp cooling

(SCSC) has been found to eectively reduce the risk of CIA in patients

(pts) exposed to Ctx for early breast cancer. However, data on SCSC in pts

with female genital tract cancer are largely lacking.

Methods: 44 pts with various female genital tract cancers who underwent

SCSC alongside to CIA-inducing Ctx were included. 35 pts had epithe-

lial ovarian and related carcinomas (79.5%), the remainder (20.5%) had

various other malignancies, mainly cervical cancer. 18 pts (40.9%) were

treated in a curative intent, 26 pts (59.1%) received palliative Ctx. 24 pts

(54.5%) had been previously exposed to Ctx. Pts were subjected to SCSC

during each Ctx cycle. CIA was quantied according to the Dean score

(DS) 3 wks aer the last Ctx cycle. Data were analyzed regarding feasibility

indicated by the SCSC completion rate, quality of hair preservation (suc-

cess: DS 0-2, failure: DS 3-4), reasons of SCSC discontinuation, and safety.

Results: 31 pts (70.5%) completed SCSC. e reasons for discontinuation

were CIA in 10 (22.7%) and adverse eects in only 3 (6.8%) pts. All side

eects, which did not exceed CTCAE grade 2, quickly resolved aer ces-

sation of SCSC. 24 pts (54.5%) experienced complete (DS 0) and 8 pts

(18.2%) had incomplete hair preservation (DS 1-2). ree pts had DS 3

(6.8%), and further 9 pts (20.5%) had DS 4. us, the overall success rate

of SCSC was 72.7%.

Conclusions: SCSC is safe and active in order to prevent CIA in pts with

female tract malignancies. Our results are particularly impressive, since

this study represent a more intensively pretreated population as enclosed

in most breast cancer studies.

Disclosure Statement: All authors declare that no conicts of interest have to be

claimed.

623

Feasibility and Satisfaction of Young Cancer Survivors

Participating in Preventive Interventions. A Subgroup

Analysis of the Care for CAYA Program (CFCP)

Simon Elmers 1; Antonia Beitzen-Heineke 1; Julia von Grundherr 1;

Wiebke Jensen 1; Barbara Koch 1; Julia Mann 1; Jannike Salchow 1;

Marianne Sinn 1; Lesley-Ann Straub 1; Luisa Wegert 1; Eik Vettorazzi 2;

Corinna Bergelt 3; Sarah Dwinger 3; Tineke Boesten 4; Gabriele Escherich 4;

Stefan Rutkowski 4; Carl Friedrich Classen 5; Charlotte Niemeyer 6;

Dirk Reinhardt 7; Jörg Faber 8; Gabriele Calaminus 9; Hermann Faller 10;

Peter U. Heuschmann 10; Jens Habermann 11; Inken Hilgendorf 12;

Markus Metzler 13; Michael Köhler 14; Petra Duhm-Harbeck 15;

Claudia Rossig 16; Stefan Bielack 17; Annette Sander 18; Sonja Schuster 13;

Thorsten Langer 15; Uta Dirksen 19; Judith Gebauer 15; Carsten Bokemeyer 1;

Alexander Stein 1

1Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center,

Hamburg, Deutschland

2Universitätsklinikum Hamburg-Eppendorf, Institut für Medizinische Biometrie

und Epidemiologie, Hamburg, Deutschland

3Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für

Medizinische Psychologie, Hamburg, Deutschland

4Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische

Hämatologie und Onkologie, Hamburg, Deutschland

5Universitätsklinikum Rostock, Rostock, Deutschland

6Universitätsklinik Freiburg, Freiburg im Breisgau, Deutschland

7Universitätsklinikum Essen, Essen, Deutschland

8Universitätsklinik Mainz, Mainz, Deutschland

9Universitätsklinikum Bonn, Bonn, Deutschland

10Uni Würzburg, Würzburg, Deutschland

11Universität zu Lübeck, Lübeck, Deutschland

12Universitätsklinikum Jena, Jena, Deutschland

13Universitätsklinikum Erlangen, Erlangen, Deutschland

14Universitätsklinikum Magdeburg, Magdeburg, Deutschland

15Universitätsklinikum Schleswig-Holstein, Schleswig-Holstein, Deutschland

16Universitätsklinikum Münster, Münster, Deutschland

17Klinikum Stuttgart – Olgahospital/Frauenklinik, Stuttgart, Deutschland

18Medizinische Hochschule Hannover, Hannover, Deutschland

19Universitätsklinikum Essen, Essen, Deutschland

Purpose: Children, Adolescents and Young Adult Cancer Survivors

(CAYA) are at in- creased risk for treatment- or disease-related late and

long-term sequelae. Follow up of large cohorts provided associations be-

tween e.g. physical activity and cardiovascular morbidity. Despite these

data, the feasibility, adherence and ecacy of specic interventions e.g. for

lifestyle modication in this patient group is unclear.

Methods: e CfC-P comprehensively assesses potential future problems

and oers dedicated preventive interventions in nutritional behavior,

physical activity and psycho-oncology (ve individual coaching sessions).

CfC-P runs in 14 centers in Germany and is supported by a research

grant from the Federal Joint Committee. Overall 1500 CAYA survivors

are planned to be included. Measures include questionnaires at baseline

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(T1) and follow-ups aer 16 (T2) and 52 weeks (T3). e patient reported

outcome measures for satisfaction was derived from the ZUF-8 question-

naire. is preliminary analysis provides patient reported data at T2 for

the subgroup of patients in Hamburg.

Results: So far about 500 survivors have been recruited in the CfC-P

since 12/2017. 127 CAYAs (57.5% female (n = 73)) of all cancer entities

(28.2% lymphoma, 26.6% carcinoma, 21.8% leukemia, 12.9% sarcoma,

10.5% other) from Hamburg were included in this analysis. Mean age was

25.9 ± 6.3 years. About half of the included patients (59 of 127) already

completed the T2-questionnaire. ZUF-8 questionnaire imply that 90.8%

of all participants rate the intervention with a high or excellent quality and

90.6% are mostly satised or satised with the program. Updated data on

satisfaction and adherence will be presented at the meeting.

Conclusions: e interventions within the CfC-P are feasible and partici-

pants report a high degree of satisfaction. Further analyses are required to

conrm these preliminary results.

650

Health Problems and Quality of Life of Young Cancer Survivors

in the Comprehensive Care for CAYA Program